motivation - Philipps-Universität Marburg

Transcription

2012
Experimentelle, klinische und kognitive
Neurowissenschaften an der
Philipps-Universität Marburg
Programm
10:00-10:30 Versammlung der Sektion Experimentelle, klinische
und kognitive Neurowissenschaften mit Wahl
des/der Sprechers/in und des/der Stellvertreters/in
10:30-12:00 Postersession mit Kurzpräsentationen ausgewählter
Vernetzungen und Initiativen
12:00-13:00 Roundtable zur Zukunft einer AG "Virtual Neuroscience Faculty“ oder einer anderen Organisationsform zur Verbesserung der fächerübergreifenden
Vernetzung der neurowissenschaftlichen Forschung
in Marburg
Ab 13 Uhr Mittagsimbiss
14-20 Uhr Allgemeines Programm des Graduiertenzentrums
"Nachmittag der Wissenschaften"
Veranstaltungsort:
Fachbereich Pharmazie, Marbacher Weg 6, Marburg
MARA (Marburg University Research Academy): http://www.uni-marburg.de/mara
MARA Neuroscience: http://www.uni-marburg.de/mara/gradcln/profil/sektionen/neuro
Sektionsmeeting
anlässlich des
„Tags der Wissenschaft“
am 17. Februar 2012
Organisation:
Martin Peper
Carsten Culmsee
Sehr geehrte Damen und Herren,
liebe Kolleginnen und Kollegen,
am 17. Februar 2012 wird wieder ein 'Tag der Wissenschaft' stattfinden. Nach dem großen
Interesse in 2011 wird es auch wieder eine Veranstaltung der Sektion "Experimentelle, klinische und kognitive Neurowissenschaften" geben.
Hier besteht für alle neurowissenschaftlichen Arbeitsgruppen - und ausdrücklich auch für
alle Nichtmitglieder der MARA-Sektion - die Möglichkeit, auf einer interdisziplinären Plattform die Projektarbeiten der eigenen Arbeitsgruppe zu präsentieren und sich über die Disziplingrenzen hinweg gegenseitig vorzustellen und auszutauschen. Die letzte Veranstaltung
hat gezeigt, dass auf diese Weise neue Kooperationen angebahnt werden können.
Die Mitarbeiterinnen und Mitarbeiter (Bachelor/Masterstudiengänge, Doktorandinnen/ Doktoranden, Postdoktorandinnen/Postdoktoranden) präsentieren Ihre Forschung wieder durch
Poster. Es sind mündliche Kurzpräsentationen vorgesehen, die dazu dienen sollen, bestehende und künftige Vernetzungen und Initiativen mit ganz konkreten Ideen zu präsentieren.
Auf diese Weise soll die Vielfalt der verschiedenen Forschungsrichtungen bezüglich gemeinsamer Initiativen gebündelt werden.
Wir möchten nochmals daran erinnern, dass alle Neurowissenschaftler Marburgs auf betreuender oder betreuter Seite aufgerufen sind, in die Sektion Neurowissenschaften der
MARA einzutreten und diese Plattform für Initiativen aktiv zu nutzen.
Unsere Initiative vom 17.01.2011 ("Virtual Neuroscience Faculty") ist als Versuch zu sehen,
durch Kopplung der Graduiertenzentrums-Sektion und einer neuen AG Synergieeffekte zu
erzielen. Es können aber auch andere wissenschaftliche Organisationsformen gewählt werden. Diese Initiative ist als "initial seed" zu sehen, die weitere Absprachen bzgl. Organisation
und Steuerungsgremium notwendig macht, um die Interessen aller Neurowissenschaften
einschließlich der Klinischen Arbeitsfelder angemessen zu berücksichtigen.
Es würde uns freuen, wenn an der Versammlung möglichst viele Kolleginnen und Kollegen
aus ALLEN Arbeitsfeldern der Neurowissenschaften teilnehmen könnten, um das weitere
Vorgehen zu besprechen. Wir laden ein, diese Gelegenheit zu nutzen, um eigene Vorstellungen einzubringen.
Im Hinblick auf die Vernetzung der Neurowissenschaftler in Marburg und bestehende sowie
zukünftige gemeinsame Initiativen bitten wir Sie, diese Information an Ihre Mitarbeiterinnen
und Mitarbeiter weiterzugeben. Bitte nutzen Sie alle diesen Nachmittag der Wissenschaft,
um die Vernetzung der Neurowissenschaften auf allen Ebenen weiter voranzubringen.
Mit freundlichen Grüßen,
Martin Peper
Carsten Culmsee
(Sektionssprecher)
2
Allgemeine Informationen
Experimentelle, klinische und kognitive Neurowissenschaften
Die MARA-Sektion „Experimentelle, klinische und kognitive Neurowissenschaften“ stellt anlässlich des „Tags der Wissenschaft“ am 17. Februar 2012 im Rahmen eines eigenen wissenschaftlichen Programms wieder aktuelle Forschungsergebnisse vor. Die unterschiedlichen
Blickwinkel der einzelnen Fächerkulturen bieten die Chance, neue Ideen für eigene Forschungsprojekte zu entwickeln sowie Kooperationspartner für interdisziplinäre Forschungsverbünde kennen zu lernen. Der „Tag der Wissenschaft“ stellt ein Forum dar, um bestehende Kontakte zu pflegen, neue Kontakte zu knüpfen und so die eigene Vernetzung an der Philipps-Universität auszubauen. Den jungen Nachwuchswissenschaftlern wird eine Möglichkeit
geboten, ihre eigenen Forschungsergebnisse zu präsentieren, interdisziplinär zu diskutieren
und dabei andere Wissenschaftler und deren Forschungsansätze kennen zu lernen.
Teilnahme
Die Teilnahme ist kostenlos. Die Veranstaltung ist als Plattform des interdisziplinären wissenschaftlichen Dialogs an der Philipps-Universität gedacht und soll durch die rege Teilnahme
vieler (Nachwuchs-)Wissenschaftler bereichert werden. Daher begrüßen wir auch gerne diejenigen, die noch keine Mitglieder im Graduiertenzentrum sind. Das Rahmenprogramm des
„Tags der Wissenschaft“ finden Sie auf der Homepage:
http://www.uni-marburg.de/mara/gradcln/aktuelles/events/programmheft_2012_1.pdf
Tagungsort
Das Sektionstreffen findet im Fachbereich Pharmazie, Marbacher Weg 6, Marburg, statt. Vor
Ort stehen 40 Posterflächen zur Verfügung. Die Poster sind entsprechend dem Präsentationsplan (siehe unten) gruppiert anzubringen (Nutzung von Vorder- und Rückseite der Stellwände). Es handelt sich um Standard-Posterwände der Universität für Tagungen, die für Poster der Größe DinA0 (Hochformat) ausgelegt sind.
Poster
Freie Vorträge sind aus Zeitgründen nicht vorgesehen. Alle unten aufgeführte Beiträge werden als Poster präsentiert und können im Rahmen der Postersession individuell diskutiert
werden. Auf den Postern werden exemplarisch Forschungsschwerpunkte und bereits bestehende Vernetzungsprojekte der Kolleginnen und Kollegen vorgestellt.
Roundtable
Abschließend sollen Möglichkeiten zur Verbesserung der fächerübergreifenden Vernetzung
der neurowissenschaftlichen Forschung und Weiterbildung in Marburg gemeinsam diskutiert
werden. Es werden bereits bestehende Initiativen vorgestellt und zukünftige Ideen zur besseren Transparenz und Vernetzung diskutiert. Hierzu werden die anwesenden Arbeitsgruppenleiter auf das Podium gebeten (Leitfragen: siehe unten).
3
10:30-12:00 Postersession
1 Molekulare und Biologische Neurowissenschaften (FB 04, FB 16, FB17, FB20)
Extracellular long-term recordings from polarization-sensitive interneurons of the locust brain
M. Bech, U. Homberg
Three dimensional reconstruction of neuropils and neurons in the central complex of the
desert locust, Schistocera gregaria
T. Bockhorst, R. Heidasch, J. Von Hadln, U. Homberg
Neuropeptides in the antennal lobes of Tribolium castaneum
M. Binzer, C. M. Heuer, J. Schachtner
Modulation of adult neurogenesis in the olfactory bulb in an acute mouse model of Parkinson’s disease
W.-H. Chiu, T. Carlsson, M. Arend, G. Höglinger, W. H. Oertel, V. Ries
Post Metamorphic Plasticity of Numbers of Peptidergic Neurons in the Antennal Lobe of Tribolium castaneum
P. Christ, S. Redelfs, M. Kollmann, J. Schachtner
Cell proliferation in the brain of the red flour beetle Tribolium castaneum
M. Diesner, P. Christ, M. Kollmann, B. Götz, J. Schachtner
Pharmacological modulation of KCa2 channels as therapeutic strategies for neurodegenerative
disorders
A. M. Dolga, R. Dodel, G. Höglinger, N. Plesnila, C. Culmsee
Neuropeptides in the mushroom bodies of Tribolium castaneum
C. M. Heuer, M. Binzer, J. Schachtner
Loss of IRF9 Prevents Lethal Lymphocytic Choriomeningitis Virus Infection in Mice at the Cost
of Viral Persistence and Chronic Inflammation in the CNS
M. J. Hofer, C. Koehler, W. Li, P. Manders, I. L. Campbell
From the antenna to the mushroom body: The olfactory pathway of the red flour beetle Tribolium castaneum
M. Kollmann, S. Dippel , S. Frank, M. Binzer, C. Heuer, S. Schütz, E. A. Wimmer, J. Schachtner
Membrane-type matrix metalloproteinases differentially promote the migration and invasion
of murine astrocytes in various in vitro assays
R. Merten, A. Voß, A. Schmidt, J.W. Bartsch, A.Pagenstecher
Enhanced Performance in a sequential reaction time task in a rat model of temporal lobe epilepsy with classic hippocampal sclerosis
B. Norwood, M. T. Eckart, J. Will, R. Schwarting, F. Rosenow
Development of novel Bid inhibitors for the treatment of neurodegenerative diseases
S. Oppermann, K. Elsaesser, C. Krasel, J. Grohm, F. Schrader, S. Glinca, M. Bünemann, G. Klebe,
M. Schlitzer, C. Culmsee
4
Morphology of two parallel visual pathways through the anterior optic tubercle of the bumblebee
K. Pfeiffer and M. Kinoshita
Quantitative Analysis of the Neuropeptide Concentration in the Antennal Lobes of Aedes aegypti
A. Reifenrath, K.P. Siju, C. Wegener, S. Neupert, J. Kahnt, B.S. Hansson, F. Hauser, R. Predel, R.
Ignell, J. Schachtner
Schädigungsmechanismen in Mitochondrien als neue therapeutische Ansatzpunkte der Neuroprotektion
C. Reuther, S. Oppermann, E.M. Öxler, A.M. Dolga, C. Culmsee
Responses of central-complex neurons of the locust to expanding shapes
R. Rosner, U. Homberg
Reduced tumor load and metastasis in vivo by targeting a metalloprotease-disintegrin,
ADAM8, in highly invasive adenocarcinomas
U. Schlomann, T. Ferdous, P. Golfi, G. Koller, T. Hagemann, M. Bossard, C. Nimsky, J.W. Bartsch
2 Klinische Neurowissenschaften (FB20): Neurochirurgie, Neurologie, Psychiatrie
Optimization on Visual Pathway Reconstruction - Initial Experience
M. H. A. Bauer, D. Kuhnt, D. Freitag, C. Nimsky
Proteomic Identification of target molecules as prognostic and therapeutic marker in human
gliomas using a new brain tumor bank
J. W. Bartsch, U. Schlomann, S. Schieber, C. Conrad, F. Dong, B. Carl, A. Pagenstecher, C. Nimsky
Contrast Properties of new Ultrasound active nanoscaled Lipid Dispersions
A. Becker, J. Brüßler, D. Kuhnt, E. Marxer, U. Bakowsky, C. Nimsky
Homogeneity of new nanoscaled Ultrasound Contrast Agents in medical Ultrasound
A. Becker, E. Marxer, J. Brüßler, U. Bakowsky, C. Nimsky
Emotion processing in Parkinson’s disease: an event-related potentials study
P. Garrido-Vásquez, M. D. Pell, S. Paulmann, B. Sehm, S. A. Kotz
Morphometric brain changes in patients with MDD
M. Stratmann, U. Dannlowski, A. Krug, T. Kircher, C. Konrad
Neural correlates of physical and social causality in patients with schizophrenia and healthy
controls: Preliminary results
K.C. Wende, A. Nagels, M. Stratmann, A. Chatterjee, T. Kircher, B. Straube
Adipositasmarker in der Risikoevaluation von Subgruppen des Schlaganfalls
Y. Winter, J. Linseisen, S. Rohrmann, O. Lanczik, P. A. Ringleb, R. Dodel, W. Oertel, J. Hebebrand,
T. Back
5
Diffusion Tensor Imaging (DTI) in idiopathic REM sleep behaviour disorder (iRBD)M. Belke, M.
M. Unger, K. Hattemer, J. T. Heverhagen, B. Keil, K. Stiasny-Kolster, F. Rosenow, N. J. Diederich,
G. Mayer, J. C. Möller, W. H. Oertel, S. Knake
3 Psychologische Neurowissenschaften (FB04):
How Stress gets in the Body – A Psychobiological Approach to the Pathophysiology of Chronic
Fatigue
J. Strahler, N. Skoluda, J. M. Doerr, U. M. Nater
Resting posterior vs. anterior EEG theta activity: temporal stability and internal consistency
M.-L. Chavanon, M. Peper
Trial-by-trial adjustments of control during selective long-term-memory retrieval are mediated
by a fronto-parietal network
J. M. Kızılırmak, P. H. Khader
Kontrolltransfer bei probabilistischen Entscheidungen: Beziehungen zu Selbsteinschätzungen
der Belohnungs und Bestrafungssensitivität
M. Peper, M.-L. Chavanon
Ultrasonic communication in rats: Effects of post-weaning social isolation on social approach
behavior and brain activity in response to playback of appetitive
D. Seffer, C. Renninger, R.K.W. Schwarting, M. Wöhr
12:00-13:00 Round Table
Die anwesenden Arbeitsgruppenleiter werden auf das Podium gebeten, um bestehende fachübergreifende Forschungsinitiativen im Bereich der Neurowissenschaften zu skizzieren. Anschließend sollen Möglichkeiten zur Verbesserung der fächerübergreifenden Vernetzung der
neurowissenschaftlichen Forschung und Weiterbildung in Marburg diskutiert werden. Folgende Leitfragen können im Vordergrund stehen:
- Welche Plattformen stehen für Austausch und Vernetzung zur Verfügung? Wie können diese
Plattformen (z.B. Neurokolloquium) in der Effizienz gesteigert werden? Könnte das Graduiertenzentrum Keimzelle einer breiteren Plattform für die gesamte neurowissenschaftliche Forschung in Marburg sein?
- Wie können Ambitionen in Bezug auf überregionale Vernetzungen in Mittelhessen, die über
die bestehenden Einzelinitiativen hinausgehen? Wie kann eine „Virtual Faculty of
Neurosciences“ Transparenz, Vernetzung und fachübergreifende Forschungsinitiativen und
Weiterbildung fördern?
- Was könnte der Nutzen eines solchen Netzwerkes sein (z.B. wiss. Austausch zwischen Wissenschaftlern unterschiedlicher Disziplinen; Sicherstellung hochwertiger Aus- und Weiterbildungsstandards; Ausgangspunkt für Forschungsanträge; Schnittstelle zur Industrie etc.)?
- Wie können existierende Einzelprogramme, Workshops und Veranstaltungen von Graduiertenschulen an der Uni Marburg innerhalb eines Netzwerkes besser verknüpft und genutzt
werden?
6
Abstracts
Extracellular long-term recordings from polarization-sensitive interneurons
of the locust brain
Miklós Bech and Uwe Homberg
Philipps-University Marburg, Dept. of Biology, Animal Physiology, D-35032 Marburg
The desert locust Schistocerca gregaria perceives polarized light with a specialized dorsal
rim area of the compound eye. For maintaining constant flight directions during long-range
migration, it potentially uses the polarization pattern of the blue sky as a compass cue. In
the brain, polarization information is passed through the optic lobe and the anterior optic
tubercle to the central complex which most likely serves as an internal sky compass (Heinze
and Homberg, 2007, Science 315:995). Because the electric field vectors (E-vectors) of the
blue sky are arranged in concentric circles around the sun, the sky polarization pattern
changes during the day like the position of the sun. Thus, for long range navigation, the
processing of polarized light information has to be time-compensated.
We performed extracellular long-term recordings from polarization-sensitive neurons of the
locust central complex using copper wire electrodes. Electrodes were inserted into the brain
while the locust was fixed vertically in the experimental setup. The animal was stimulated
with polarized blue light (465 nm), obtained by an LED. The blue light passed a motor-driven
rotating polarizer, which was set on a perimeter apparatus. It allowed stimulation with a
rotating E-vector from different elevations in the visual field. The receptive field of the recorded neuron was tested every hour by stimulation through a clockwise and counterclockwise rotating polarizer (rotating speed of 30°/s). The recordings lasted for up to 24
hours. Single units were identified through template matching combined with a cluster
analysis.
The units showed polarization-opponency and had wide receptive fields over a range up to
180° along the left-right meridian. Within the visual field, E-vector tuning was not constant
but changed considerably along the right-left meridian. In addition, changes in response
amplitude and E-vector tuning depending on the time of day were observed. Several recorded units showed strong excitation or inhibition when the light source was shifted along
the right-left meridian in the visual field of the locust suggesting directionally-specific motion sensitivity. Comparison of the physiological characteristics of the recorded units with
data from previous intracellular recordings allowed for an assessment of the recorded cell
types. Supported by DFG grant HO 950/21-1.
7
Three-dimensional reconstruction of neuropils and neurons in the central
complex of the desert locust, Schistocerca gregaria
Tobias Bockhorst, Ronny Heidasch, Joss von Hadeln and Uwe Homberg
Philipps-University Marburg, Dept. of Animal Physiology, Karl-von-Frisch-Strasse 8, 35032 Marburg,
Germany
The central complex is a set of midline-spanning neuropils in the insect brain. It has become
a key model in arthropod neuroscience both for its strikingly regular neuroarchitecture and
for its increasingly apparent role in motor control and visual integration, in particular visual
place learning and spatial orientation. To analyze the neural connectivities in the central
complex we have started to reconstruct individually stained neurons in 3 dimensions for
later incorporation into a 3D standard central complex of the brain of the desert locust.
We defined external borders and internal subdivisions of central-complex subunits based on
immunohistological stainings of brain slices against the presynaptic vesicle protein synapsin
and neurotransmitters. For visualization of single-cell morphologies, the tracer Neurobiotin
was injected after intracellular recording of a given neuron’s activity during presentations of
different visual signals to the insect.
Three-dimensional reconstructions were generated from digital image stacks obtained by
confocal fluorescence microscopy and compared across different specimens for three main
purposes: (i) identification and standardization of conserved patterns in gross insect brain
anatomy (ii) typing of neurons with respect to locations of somata, branching patterns and
putative polarity (iii) identification of likely partner neurons in neural networks by coregistration of single-cell reconstructions into a standardized brain atlas.
In a second step we will compare morphological data from (ii) and (iii) with electrophysiological data to determine whether a given neuron’s responses to certain stimuli are consistent with those of its putative partners in the neural network. Furthermore, we investigate
whether branching pattern and tuning to visual stimulus features covary systematically between different subtypes of a given type of neuron, thus implementing computational or
topographical maps.
8
Marlene Binzer, Carsten M. Heuer, Joachim Schachtner
Dept. Biology, Animal Physiology, Philipps-University Marburg, 35032 Marburg, Germany
From an evolutionary perspective, olfaction represents the most ancient of the senses and
it is one of the most important ways of interaction with the environment for the majority of
metazoan animals. In insects, the antennal lobes (ALs) act as primary olfactory centers that
receive direct input from olfactory receptor neurons. While these paired deutocerebral
neuropils are also intimately linked to higher integrative centers such as the mushroom bodies, early processing and modification of olfactory signals already occurs at the level of the
olfactory glomeruli that reside within the ALs.
Beyond classical neurotransmitters like acetylcholine and γ-aminobutyric acid, studies in
different insect species have revealed AL neurons to express a variety of different neuropeptides. Representing the largest and most diverse group of neuroactive substances, neuropeptides are often considered to act as cotransmitters that are released in concert with a
principal transmitter, thereby modulating the activity pattern of a neuronal circuit.
To illuminate the potential role of neuropeptides in the AL, we investigate the neuropeptidergic repertoire of these neuropils in the emerging model organism T. castaneum. To assess the full range of the AL neuropeptidome, isolated AL tissue samples are subjected to
MALDI-TOF mass spectrometry by direct peptide profiling. Immunohistochemical stainings
are used to confirm the presence of neuropeptide transmitters and to localize sites of expression in the ALs of T. castaneum.
Supported by the DFG priority program 1392 “Integrative Analysis of Olfaction“ (SCHA
678/13-1)
9
Modulation of adult neurogenesis in the olfactory bulb in an acute mouse
model of Parkinson’s disease
Wei-Hua Chiu, Thomas Carlsson, Martin Arend, Günter Höglinger, Wolfgang H. Oertel, Vincent Ries
Department of Neurology, Philipps-University, Marburg, Germany
There is experimental evidence that dopamine controls the proliferation of neural progenitor cells in the subventricular zone (SVZ) and the hippocampal dentate gyrus. Most newborn
cells of the SVZ migrate to the olfactory bulb (OB) to form new neurons. The aim of the present study was to investigate, whether treatment with selegiline and/or L-dopa can modulate these structural changes in an acute mouse model of PD.
Adult mice received an intranigral injection with 6-Hydroxydopamine (6OHDA) unilaterally.
After 3 weeks mice were treated with selegiline and/or L-dopa for a period of 4 weeks. We
analyzed the number of BrdU+ profiles and characterized the neuronal identity of the newly
generated cells by using confocal scanning laser microscopy.
The majority of SVZ-derived newly generated cells integrate within the granule cell layer.
We determined the number of BrdU+ cells in both the granule cell layer and the glomerular
layer and their neuronal differentiation. Neurons represented the majority of newly generated cells in both layers. BrdU+ cell numbers significantly decreased on the lesioned side of
untreated mice after 6OHDA. In the different treatment groups, we found a further decrease in the number of BrdU+ profiles in the selegiline treated group, whereas L-dopa
treated mice showed a significant increase compared to the lesioned animals and the other
treatment groups in both layers.
It might be possible to modulate proliferation in the SVZ/OB system by different treatment
regimens. However, it still remains to be determined, whether an excess of new neurons
will be advantageous for olfactory function.
Keywords: Parkinson’s disease, neurogenesis, olfactory dysfunction.
10
Post Metamorphic Plasticity of Numbers of Peptidergic Neurons in the Antennal Lobe of Tribolium castaneum
The major pest of stored grain, the red flour beetle Tribolium castaneum is emerging as a
further standard insect model organism beside Drosophila. With the fully sequenced genome and its susceptibility for powerful reverse genetics based on systemic RNAinterference (RNAi), T. castaneum offers an excellent system to study development and plasticity.
Recent studies revealed an increase of brain size incl. antennal lobes (AL) and mushroom
bodies (MB) within the first days of adult life, indicating a pronounced sensitive phase.
To further reveal mechanisms involved in the post metamorphic phase, we examined
whether there are changes in the number of peptidergic AL cells. We compared the numbers of tachykinin-ir (TK-ir) AL neurons of females and males directly after adult molt (A0)
and seven days after molt (A7). We found (1) a sexual dimorphism at A0 concerning numbers of TK-ir cells, with females having more TK-ir AL neurons than males. (2) In both sexes,
the numbers of AL TK-ir cells increased from A0 to A7. Females, isolated shortly before adult
molt, showed no increase in the number of TK-ir cells, in contrast to males held under same
conditions. This phenotype can be rescued by addition of the aggregation and sex pheromone 4,8-Dimethlydecanal (DMD). High doses of DMD also have an effect on TK-ir numbers
in male Tribolium. Our finding suggests, the increase of TK-ir cells between A0 and A7 in
females depends on the perception of the pheromone signal and thus favors an activity
dependent mechanism for the maturation of a peptidergic system in the AL of Tribolium.
678/13-1)
11
Tribolium castaneum is emerging as a further standard insect model besides Drosophila.
With the fully sequenced genome, its susceptibility for transgenetic approaches such as
directed gene expression and powerful reverse genetics based on systemic RNA interference, and its longevity, Tribolium offers an excellent system to study development and
plasticity of the olfactory system.
Studies in several arthropod species demonstrated a correlation of cell proliferation rate or
volumes of brain areas with age, caste, sex, and experience, including primary sensory integration centers like optic lobes and antennal lobes / olfactory lobes, but also higher integration centers like the mushroom bodies (MB).
To further examine mechanisms involved in brain plasticity of the red flour beetle Tribolium
castaneum within the first days of adult life, we started to study cell proliferation using the
cell proliferation marker α-Phospho-Histone-3 (α PH3), labeling proliferating cells during
end of G2 phase and begin of the metaphase. We used α PH3 in combination with several
markers to label cell nuclei (DAPI), glial cells (anti reverses polarity – α RePo) and neuronal
cells (anti horse radish peroxidase – α HRP) to determinate identity of proliferating cells.
Proliferating cells could be observed not only in the MB calyces but interestingly also in the
area of the optical lobes (OL) and antennal lobes (AL).
678/13-1)
12
Pharmacological modulation of KCa2 channels as therapeutic strategies for
neurodegenerative disorders
1
Dolga AM, 2Dodel R, 2Höglinger G, 3Plesnila N, 1Culmsee C
1
Institute of Pharmacology and Clinical Pharmacy, Karl von Frisch Straße 1, 35043, University of Marburg,
2
3
Germany, Department of Neurology, University of Marburg, 35043, Marburg, Germany, Institute of Stroke
and Dementia Research, University of Munich Medical School, Munich, D-81377, Germany
Potassium channels are widely expressed and are the most diverse class of ion channels.
These transmembrane channels play critical roles in physiological functions of the cell and
under pathophysiological conditions. Previous studies demonstrated that regulation of several vital cell functions, such as calcium homeostasis, excitability and survival can be
achieved by modulation of NMDAR activity through small conductance calcium-activated
potassium (KCa2/SK) channels. In neurons, activation of KCNN/SK/KCa2 channels significantly
reduced pathological increases in [Ca2+]i and maintain calcium homeostasis after NMDA
receptor activation. Their activation also reduces excitotoxic neuronal death in vitro and in
vivo in a model of cerebral artery occlusion. Hitherto, these KCa2/SK channels were shown
to be localized exclusively to dendritic spines. We identify for the first time additional localization of KCa2.2 channels at the inner mitochondrial membranes. Activation of these mitochondrial KCa2.2 channels mediates sustained neuroprotection by inhibiting mitochondrial
fragmentation process, loss of mitochondrial membrane potential and AIF translocation to
the nucleus. Besides functional activities at neuronal sites, we found that positive pharmacological activation of KCa2/SK channels significantly reduced LPS-stimulated activation of
microglia and the downstream events including TNF-6 cytokine production and NO
release. All together, these data demonstrate that KCa2 channels elicit a dual mechanism of
action with neuroprotective properties for neuronal cells and inhibition of inflammatory
markers in microglial cells, suggesting novel insights and therapeutic strategies for modulation of neurodegeneration and immune-related CNS diseases.
13
Carsten M. Heuer, Marlene Binzer, Joachim Schachtner
Biology, Animal Physiology, Philipps-University Marburg, 35032 Marburg, Germany
Neuropeptides are a highly diverse group of signaling molecules that affect a broad range of
biological processes in insects, including development, metabolism, behavior, and reproduction. In the central nervous system, neuropeptides are usually considered to act as neuromodulators and co-transmitters that modify the effect of ‘classical’ transmitters at the
synapse, thus shaping activity and output patterns of neuronal circuits. While neuropeptides have been shown to play key roles in regulating endocrine events and coordinating
behavioral actions, they are also thought to be involved in processes related to neuronal
plasticity, the substrate for learning and memory.
Mushroom bodies (MBs) are prominent neuropils of the insect brain that are often regarded as principal sites of learning and memory. Probably of ancient evolutionary origin,
these integrative brain centers are intimately connected with primary olfactory neuropils
but may also receive information from other sensory modalities. In the red flour beetle T.
castaneum, the MBs comprise a single knob-shaped calyx, a stalk-like peduncle, and a
medial and vertical lobe, each consisting of distinct subdivisions. The whole structure is
formed by dendritic and axonal processes of intrinsic MB neurons, the Kenyon cells.
Studies in a variety of insects have demonstrated the presence of different neuropeptides in
either intrinsic or extrinsic MB neurons, suggesting this group of signaling molecules to play
an important role in information processing in the MBs. To further elucidate these functions, we investigate the neuropeptide repertoire of the MBs in the coleopteran model organism T. castaneum. Neuropeptide distribution is examined in immunohistological preparations using confocal laser scanning microscopy. To assess the full range of the MB neuropeptidome, isolated MB tissue is analyzed by means of MALDI-TOF mass spectrometry. The
findings are compared to other insect species, including holometabolous and hemimetabolous taxa, as well as ancestral representatives.
Supported by the DFG priority program 1392 “Integrative Analysis of Olfaction” (SCHA
678/13-1)
14
Loss of IRF9 Prevents Lethal Lymphocytic Choriomeningitis Virus Infection in
Mice at the Cost of Viral Persistence and Chronic Inflammation in the CNS
Hofer MJ1,2, Koehler C1, Li W2, Manders P2, and Campbell IL2
1
2
Dept. of Neuropathology, University of Marburg, Germany
School of Molecular Bioscience, University of Sydney, NSW, Australia
Functional type I interferon (IFN) signaling is critical for the host response to viruses. Cellular responses to type I IFNs depend largely on STAT1, STAT2 and IRF9. Here we studied the
effects of IRF9-deficiency on the host response to a viral infection in the CNS. Wild-type
(WT) mice and mice lacking IRF9 (IRF9 KO) were infected intracranially with lymphocytic
choriomeningitis virus (LCMV). In WT mice, a lethal lymphocytic choriomeningitis (LCM)
occurred by day 7 with characteristic cerebral seizures and LCMV being largely confined to
the CNS. In contrast, LCMV-infection of IRF9 KO mice caused a transient non-fatal clinical
disease and virus spread to peripheral organs. Viral RNA levels decreased slowly over time
and became undetectable in some peripheral organs such as liver and spleen but remained
detectable in the CNS for more than 150 days. In the CNS, sites of viral infection were associated with foci of activated microglia / macrophages, multi-nucleated giant cells and moderate T-cell infiltrates. The presence of virus and immune pathology in the CNS and peripheral organs was paralleled by significantly increased expression of various cytokine
mRNAs, including IFN-g and TNF, as well as of the co-inhibitory molecule B7-H1 (PD-L1 or
CD274) mRNA. In conclusion, these findings indicate that the absence of IRF9 prevents lethal LCM but results in persistent infection and chronic inflammation in the CNS. The presence of T-cells and the slow decrease in viral RNA levels in the CNS and peripheral organs
argue for a retarded rather than an exhausted or incapacitated anti-viral response.
15
From the antenna to the mushroom body: The olfactory pathway of the red
flour beetle Tribolium castaneum
M. Kollmann1, S. Dippel2,3, S. Frank1, M. Binzer1, C. Heuer1, S. Schütz3, E. A. Wimmer2, J.
Schachtner1
1
2
Dept. Biology, Animal Physiology, Philipps-University Marburg, 35032 Marburg, Germany. Dept. Developmental Biology, Johann-Friedrich-Blumenbach- Institute of Zoology and Anthropology, Georg-August3
University Göttingen, 37077 Göttingen, Germany. Dept. Forest Zoology and Forest Conservation, GeorgAugust-University Göttingen, 37077 Göttingen, Germany
The olfactory pathway of insect starts with the olfactory receptor neurons (ORNs) in the
chemoreceptor sensilla of the antenna, which project into the glomeruli of the antennal
lobe (AL). From the AL, projection neurons connect to the higher integration centers, the
mushroom body (MB) and the lateral protocerebrum or lateral horn.
By creating and analyzing a Gal4-UAS line, expressing tGFP in all ORNs, which contain the
Orco (the general olfactory receptor), electron raster microscopy of the antenna, immunostainings of the brain, backfills of the antenna and maxillary palps and 3D reconstruction we
characterized the olfactory pathway of T. castaneum in high detail.
We were able du characterize several sensilla types, like the chemosensitive large and small
s. basiconica and s. trichoidea, which express Orco, or the mechanoreceptive s. chaetica
which does not express Orco. Axons of ORNs express the Orco projecting only into about
50% of the AL glomeruli of the lateral half of the AL. We analyzed the anatomical fetchers of
the pathway and couldn’t find any sexual dimorphism at the level of the antenna and the
AL. By using backfills we could describe the antenno-protocerebral tract. We also backfilled
projections from the antenna to the accessory medulla of the optical lobes, something that
had never been observed before in insects, while the backfills of the maxillary palps labeld
only one glomeruli in the AL.
supported by the DFG: SPP 1392, SCHA 678/13-1, SPP 1027: Wi 1797/2-2 and Schu 1135/8-1
16
Membrane-type matrix metalloproteinases differentially promote the migration and invasion of murine astrocytes in various in vitro assays
Raphael Merten1, Andreas Voß1, Ansgar Schmidt3, Jörg W. Bartsch2, Axel Pagenstecher1
1
2
3
Department of Neuropathology , Clinic of Neurosurgery and Department of Pathology , University of Marburg,
35043 Marburg, Germany
Membrane-type matrix metalloproteinases (MT-MMPs1-6) are membrane-bound proteins
with important functions in many physiological and pathological processes. These MTMMPs have matrix-degrading and sheddase activities and are upregulated in several types of
gliomas. Since certain MT-MMPs advance the migration and invasion of tumour cells we studied the potential of MT-MMPs to promote astrocytic migration and invasiveness using different virally-transduced stable cell-lines of murine p53-/- astrocytes each expressing one of
the six human MT-MMPs. Transgene expression was verified by RNase-Protection-Assay and
Western blotting. The capability for invasion and migration of transduced astrocytes was
determined by scratch-, matrigel invasion- and a novel assay based on organotypic slice cultures. In contrast to many conventional assays such as matrigel invasion chambers, however,
our novel method employs CNS tissue as the substrate for the migration and invasion of
cells.
In all assays employed, MT-MMP transduced astrocytes migrated or invaded better than
astrocytes transduced with only control vector, although to a different extent. In scratch and
matrigel assays, MT1-MMP was the strongest enhancer of migration and invasion, and to a
lesser extent, MT5-MMP and MT6-MMP. However, when the invasive capability of MT-MMP
expressing astrocytes was assessed in organotypic slice cultures, MT6-MMP mediated the
strongest infiltration potential of astrocytes. These results demonstrate 1. that all MT-MMPs
are differentially potent mediators of astrocyte migration and infiltration in CNS tissue and 2.
that it is pivotal to use an authentic CNS substrate for migration in order to evaluate the particular role of proteases in astrocytic infiltration. In conclusion, we have shown an unexpectedly high potential of MT6-MMP over MT1-MMP to enhance invasion and migration of murine astrocytes in the central nervous system which could affect glioma progression and infiltration.
Supported by the Wilhelm-Sander-Stiftung
17
Enhanced Performance in a sequential reaction time task in a rat model
of temporal lobe epilepsy with classic hippocampal sclerosis
Braxton Norwood, Moritz Thede Eckart, Johanna Will, Rainer Schwarting, Felix Rosenow
UKGM, Epilepsiezentrum Hessen
FB Psychologie, AG Verhaltensneurowissenschaft
In 1987 Nissen and Bullemer introduced their human serial reaction time task (SRTT) to
study the neural basis of sequential learning (a subcategory of procedural/ implicit learning). In this task, subjects respond to visual stimuli by keypressing. Stimuli are presented in
either a sequential or random fashion. Reaction time (RT) typically increases when the stimulus presentation switches from a previously trained sequence to random stimulus presentation (termed interference effect).
It is well documented, in both human and animal research, that striatal dopaminergic
processes play a major role in the acquisition of sequential behavior. However, findings on
the role of the hippocampus – which is mainly associated with declarative memory – and
especially the interplay between hippocampus and striatum in sequential learning, are less
univocal.
Three major hypotheses exist concerning the interplay between hippocampus and striatum:
1. both structures interact; 2. they work dissociated; 3. they compete.
Empirical support exists for all three hypotheses.
In a previous experiment rats with dorsal hippocampal ibotenic acid lesions showed a superior SRTT performance in terms of faster reaction times and lower error rates.
In the present study we tested the effects of perforant pathway stimulation-induced hippocampal neurodegeneration on sequential learning in the SRTT. The selected paradigm immediately produces extensive, but focused hippocampal neurodegeneration that leads to
classical hippocampal sclerosis and spontaneous hippocampal-onset seizures approximately
three weeks after stimulation
This experiment was conducted to replicate the effect of superior SRTT performance in hippocampal lesioned rats and to determine whether hippocampal lesions have a direct or
indirect (e.g. via generally enhanced instrumental learning) effect on sequential learning.
Both control and lesioned animals showed an expected interference effect of slower RTs
and higher error rates during random, when compared to sequential, stimulus presentation.
Of special interest is the observation that lesioned animals had a superior SRTT performance when compared to controls, indicating that hippocampal lesions cause superior instrumental learning.
18
Oppermann S.1, Elsaesser K.1,Krasel C.1, Grohm J.1, Schrader F.2, Glinca S.2, Bünemann M.1, Klebe G.2, Schlitzer M.2, Culmsee C.1
1
Institut für Pharmakologie und Klinische Pharmazie, Phillips Universität Marburg, Karl-von-Frischstr.
1, 35032 Marburg, Germany
2
Institut für Pharmazeutische Chemie, Marbacher Weg 6-10, 35032 Marburg, Germany
Mitochondrial pathways of apoptosis are major features of neuronal death after
acute brain damage and in neurodegenerative diseases, such as Alzheimer’s disease
and Parkinson’s disease. The Bcl-2 protein Bid is a key player in these mechanisms,
causing mitochondrial dysfunction and detrimental release of pro-apoptotic proteins into the cytosol. Previous studies showed that small molecule Bid inhibitors
such as BI6c9 effectively prevent neuronal cell death in vitro. In vivo, however, the
available Bid-inhibitors failed to protect brain tissue likely because the compounds
were not bioavailable and did not cross the blood brain barrier. Therefore, the aim
of the present study is the development of novel, potent Bid inhibitors which are
neuroprotective and available for applications in model systems of brain damage in
vivo. In a first approach, chemical modifications of BI-6c9 were performed resulting
in modified structures and new molecules with different pharmacophors.
The first screening of these 50 compounds addressed their ability to prevent glutamate induced cell death compared to BI-6c9 in immortalized mouse hippocampal
neurons (HT-22 cells). In this model system, glutamate induces a decrease of intracellular glutathione levels resulting in lipoxygenase activity and enhanced formation
of toxic reactive oxygen species (ROS). Bid siRNA and small molecule inhibitors of
Bid prevented the following mitochondrial damage and cell death, suggesting that
Bid was a key player in the cascade of cell death signaling in this model system.
We applied the xCELLigence System, which allows continuous real-time monitoring
of cell viability to determine neuroprotective potency of the newly synthesized
structures. In this system seven of the tested compounds significantly attenuated
cell death by glutamate. In addition, we used the MTT- assay to confirm the protective effects of the protective compounds.
In conclusion, we were able to identify seven new molecules with different structures that provided protective effects in the model of glutamate toxicity in HT-22
cells. Next steps of the project include further optimization of the identified structures and analyses of their binding to the pro-apoptotic protein Bid. Therefore recombinant Bid and t-Bid are expressed and purified from a pET 15b plasmid construct for co-crystallization of available and novel structures with the Bid protein as
a basis for improved design of neuroprotective Bid inhibitors for therapy studies in
models of neurodegenerative diseases.
19
Morphology of two parallel visual pathways through the anterior optic tubercle of the
bumblebee
Keram Pfeiffer and Michiyo Kinoshita
The anterior optic tubercle (AOTu) is a small neuropil in the protocerebrum of insects and a
prominent projection area of visual interneurons from the optic lobe. It consists of an upper
subunit of yet unknown function and a lower subunit that is part of the sky-compass system
in
desert locusts. While in crickets and locusts a multitude of neurons within the sky-compass
system have been characterized, the hymenopteran sky-compass has been almost exclusively
studied at the behavioral level.
Here we studied the morphology of the AOTu of the bumblebee (Bombus ignitus) in serial
semi-thin frontal sections stained with Azur II and its neural connections through injection of
biotinylated dextran.
Like in other insects, the AOTu of Bombus comprised two subunits. The small lower
subunit sat on the posterior lateral side of the upper subunit.
Through dextran injection we traced two parallel pathways from the compound eye through
the AOTu to the central brain. Both pathways ran via the serpentine layer of the medulla,
through the lobula to the lateral accessory lobe and included branches in the contralateral
AOTu. Staining patterns after injection into the lower subunit or the upper subunit,
respectively, were distinctly different and showed no overlap.
While dye application to the most dorsal aspect of the posterior medulla, (the target of long
visual fibers from the dorsal rim of the compound eye) revealed projections only in the lower
subunit of the AOTu, tracer application to the most ventral part of the medulla labeled the
dorsal part of the AOTu’ s upper unit.
Most neurons of both pathways showed remarkable similarity to those described in the locust.
Most prominently, medulla tangential neurons projecting to the lower subunit had extensive
branches in the most dorsal area of the posterior medulla, and projections from the AOTu’ s
lower subunit terminated as glomerular structures in the lateral accessory lobe, resembling
polarization-sensitive TuLAL neurons of the locust.
20
Quantitative Analysis of the Neuropeptide Concentration in the Antennal
Lobes of
Aedes aegypti
A. Reifenrath1, K.P. Siju2, C. Wegener1, S. Neupert3, J. Kahnt4, B.S. Hansson5, F. Hauser6, R.
Predel3, R. Ignell2, J. Schachtner1
1
2
Dept. Biology, Animal Physiology, Philipps-University Marburg, 35032 Marburg, Germany. Div. Chem. Ecol.,
3
Dept. Plant. Prot. Biol., Swedish University of Agricultural Sciences, Alnarp, Sweden. Dept. Zoology, Biocentre,
4
University of Cologne, 50674 Cologne, Germany. Max Plank Institute for Terrestrial Microbiology, 35043 Mar5
burg, Germany. Dept. Evol. Neuroethol., Max Planck Institute for Chemical Ecology, 07745 Jena, Germany.
6
Center Funct. Comp.Insect Genomics, Dept. Cell. Biol. and Comp. Zool., Inst. Biol., University of Copenhagen,
Denmark
The yellow fever mosquito, Aedes aegypti, is the major vector of several arboviral diseases,
e.g. dengue fever and yellow fever. The gonotrophic cycle of Ae. aegypti females consists of
distinct behavioral and physiological phases, including host seeking, blood feeding and oviposition. These changes in behavior depend on changes in the processing of sensory information, especially the processing of olfactory information. A multitude of chemical signaling
molecules modulates processing of odor information in the central nervous system, including the primary olfactory centers of insects, the antennal lobes. The most occurring and
diverse group of neuromodulators, in vertebrates and invertebrates, are the neuropeptides.
In the present study we analyzed the diversity of neuropeptides in the antennal lobe of Ae.
Aegypti in quantity and quality in different stages during the gonotrophic cycle using direct
MALDI-TOF mass spectrometric peptide profiling. For this, we compare neuropeptide mass
spectra of Ae. aegypti females before and different periods after blood feeding, and after
oviposition. For a quantitative analyzes of changes in the concentration of specific neuropeptides we use isotope labeled peptides as internal standards.
21
Schädigungsmechanismen in Mitochondrien als neue therapeutische Ansatzpunkte der Neuroprotektion
Institut für Pharmakologie und Klinische Pharmazie, Biochemisch-Pharmakologisches Centrum Marburg, Philipps-Universität Marburg
Die Arbeitsgruppe von Prof. Dr. Carsten Culmsee forscht an molekularen Mechanismen des
neuronalen Zelltods in Modellsystemen neurodegenerativer Erkrankungen. Im Fokus der
Untersuchungen stehen pathologische Veränderungen in Mitochondrien, die durch
oxidativen Stress und eine gestörte Calcium-Homöostase verursacht werden. Die Ziele der
Forschungsarbeiten sind neue therapeutische Ansatzpunkte nach akuter Hirnschädigung
durch Schlaganfall und bei neurodegenerativen Erkrankungen wie Morbus Alzheimer und
Morbus Parkinson.
Auf dem Übersichtsposter werden laufende Projekte vorgestellt, in denen die Mechanismen
der morphologischen Veränderungen von Mitochondrien nach Schädigung von Neuronen
durch oxidativen Stress untersucht werden. Hier kommt es in den Neuronen durch die Aktivierung von Lipoxygenasen und der GTPase Dynamin related protein 1 (Drp1) zur Fragmentierung der Mitochondrien sowie zur Translokation des pro-apoptotischen bcl-2 Proteins
Bid. Aktiviertes Bid und Drp1 vermitteln gemeinsam den Verlust der Membranintegrität in
den Mitochondrien und die Freisetzung des „Apoptose induzierenden Faktors“ (AIF). Neue
pharmakologische Inhibitoren von Bid oder Drp1 verhindern die morphologischen und funktionellen Schädigungen der Mitochondrien und können so Neurone vor dem Zelltod bewahren. Auch die Hemmung der AIF-Translokation von Mitochondrien in den Zellkern durch
siRNA- oder Mutation-bedingten AIF-knock down zeigt in Zellkulturen und in vivo
neuroprotektive Wirkungen. Ähnliche protektive Effekte werden durch Inhibitoren des AIFBindungspartners Cyclophilin A oder siRNA-vermittelte CypA-Expressionshemmung erreicht,
die Mitochondrien und Neurone gegen oxidativen Stress schützen. Auch die Erhaltung der
Calciumhomöostase durch neue Kaliumkanalaktivatoren, die nach neuesten Erkenntnissen
ihre Wirkung an der Zellmembran und in den Mitochondrien entfalten, ist eine wirkungsvolle Strategie, um über Mitoprotektion eine neuroprotektive Wirkung in vitro und in vivo zu
vermitteln.
Die Arbeiten der AG Culmsee zeigen in den verschiedenen Projekten neue Strategien auf,
wie über den Schutz von Mitochondrien eine neuroprotektive Wirkung erreicht werden
kann. Neue Leitstrukturen für Therapeutika, die an den molekularen Mechanismen der
Mitochondrienschädigung angreifen sind daher vielversprechend für neue protektive Strategien nach akuter Hirnschädigung sowie bei neurodegenerativen Erkrankungen.
22
Responses of central-complex neurons of the locust to expanding shapes
Ronny Rosner1, Uwe Homberg1
1
Philipps-Universität Marburg, Tierphysiologie, Karl-von-Frisch-Straße 8, D-35032 Marburg, Germany
The central complex (CC) is a prominent structure in the brain of insects and is thought to
play an important role in spatial orientation, spatial memory, and motivation for locomotion.
Lesions of the CC lead to motor deficits comparable to those seen in vertebrates with lesions
in the cerebellum (Strausfeld 2009, Proc R Soc Lond B Bio Sci 276: 1929-1937). Evidence is
accumulating that the CC is the main brain structure in insects that (i) integrates sensory
information about where in the spatial surround a particular event occurs, (ii) determines in
which direction the animal is currently moving, and (iii) generates the motor commands determining the to-be direction of locomotion.
Work on the sensory input in the locust CC so far mainly concentrated on the responsiveness
to polarized light. Polarized light information is thought to be used by the animals to indirectly determine the position of the sun in the sky. A widespread network of neurons within
particular parts of the CC was found to process this kind of information. However large parts
of the CC seem to be non responsive to polarized light. We aimed to find out whether these
structures process unpolarized visual stimuli in the locust Schistocerca gregaria. Intracellular
recordings showed that many neurons of the CC were highly sensitive to looming stimuli
mimicking approaching objects on a direct collision course. We also found responses to small
translating squares. Some of the tested neurons were inhibited by the looming stimulus presented to one eye of the locust but were excited when the stimulus was experienced by the
opposite eye. These properties suggest azimuth dependence of the neuronal responses with
respect to approaching objects. Thus, the central complex may serve as the neuronal correlate for hiding responses seen in locusts (Hassenstein and Hustert 1999, J Exp Biol 202:17011710) or directional escape behavior found in Drosophila (Card and Dickinson 2008, Curr Biol
18:1300-1307) elicited by similar stimuli.
Surprisingly to us the responses to visual motion and in particular to looming stimuli were
not restricted to those neurons of the CC that are not polarization sensitive. Instead neurons
throughout all substructures of the CC were responsive. This indicates that looming sensitivity is even more widespread in the locust central complex than the responsiveness to polarized light.
Supported by DFG grant HO 950/16-2
23
Reduced tumor load and metastasis in vivo by targeting a metalloprotease-disintegrin, ADAM8, in highly invasive adenocarcinomas
Uwe Schlomann1,3, Taheera Ferdous1, Panagiota Golfi1, Garrit Koller1, Thorsten
Hagemann2,
Maud Bossard2, Christopher Nimsky3, Jörg W. Bartsch1,3.
1
IPS, King’s College London, UK; 2,Queen Mary Univ. London, UK; 3Marburg University,
Germany.
ADAM proteases (A Disintegrin And Metalloprotease Domain) are multi domain
proteases with functions in tumor cell growth, cell adhesion and ECM remodeling. High expression levels of ADAM8 are correlated with bad patient prognosis
in brain, lung, and pancreatic cancer. The objective of this study was to validate
ADAM8 as drug target in adenocarcinomas. In pancreatic tumor cells Panc1,
ADAM8 overexpression (Panc1/A8) leads to increased cell migration and cleavage of fibronectin and collagen I and IV, causing enhanced invasion into the
ECM via ADAM8. In Panc1/A8 cells, ADAM8 interacts with ß1 integrin, activating
ERK, Akt and p38 pathways. Panc1/A8 cells were grafted orthotopically into pancreas of nude mice. Larger tumors were found from Panc1/A8 cells compared to
control cells. More importantly, higher metastatic load from these cells in liver
and spleen was observed. As therapy approach, we designed a cyclic peptide
(“cycP1”) mimicking the integrin binding loop of ADAM8. CycP1 impedes
ADAM8- 1 integrin interactions causing reduced intracellular signaling. In vivo,
cycP1 is very potent (IC50 ~ 70nM) in reducing tumor load and formation of metastases compared to untreated mice. Our results suggest that inhibition of
ADAM8 in highly invasive adenocarcinomas is feasible for therapeutic intervention and provides a solid basis for further preclinical drug development with
special emphasis on therapy of gliomas. Supported by Cancer Research Technology, UK.
24
Miriam H. A. Bauer, Daniela Kuhnt, Dennik Freitag, Christopher Nimsky
Department of Neurosurgery, University of Marburg, Baldingerstrasse, 35033 Marburg, Germany
Introduction: Diffusion Tensor Imaging (DTI) based fiber tractography enables the visualization of fiber bundles in the intraoperative setting of neurosurgical operations and contributes to minimized postoperative morbidity 2,4. Large fiber bundles like the corticospinal
tract can easily be visualized. Other fiber bundles like the visual pathway, the arcuate fasciculus or small fiber tracts are hard to visualize reliably. In case of the visual pathways, artifacts due to its close relation to the skull base, its small diameter, strong curvature in Meyer's Loop and discontinuity in lateral geniculate body contribute to its difficult visualization1,3. Additionally, there is no consensus regarding best acquisition parameters for DTI,
seed region placement and interpretation of the results5.
Methods: For a first impression on the influence of sequence parameterization, different DTI
acquisitions were performed besides the local standard for DTI measurements. All data sets
were acquired from 16 year old patient dealing with a left occipital DNET on a 3T Siemens
Trio, using a 12 channel head coil. Four different acquisition schemes were applied differing
in voxel size, voxel shape and image alignment. Additionally 3D T1- and 3D T2-weighted images were acquired.
Tensor deflection based fiber tractography was performed to reconstruct the visual pathway
with different seed regions to visualize optic nerve, chiasm, optic tract and optic radiation.
After image fusion and skull stripping also fractional anisotropy and relative anisotropy were
measured for the whole brain.
Results: Data sets with similar voxel volume, but different voxel shape and different image
alignment (AC-PC-oriented or parallel to the optic nerve) showed similar results in both anisotropy histograms. Images with reduced voxel volume delivered deviation results on both
anisotropy histograms and also ended in poor reconstruction results on visual inspection
(missing ground truth). Image alignment seems to influence the reconstruction, where acquisition alignment along the optic nerve delivers better fiber tracking results (larger bundles, symmetric, homogeneous anisotropy values) on visual inspection.
Discussion: The initial experiments on optimization of DTI acquisition for visual pathway reconstruction show that image alignment influences the reconstruction results, where alignment parallel to the optic nerve seems to deliver better and more symmetric results. Our
experiments are now enlarged by systematic parameter varying image acquisition of healthy
volunteers for optimization of visual pathway reconstruction using the 12 channel and the
32 channel head coil, to identify promising sequences in comparison with the local standard
DTI sequence that will finally be evaluated with patients dealing with lesions along the visual
pathway or temporal lobe epilepsy who undergo navigated surgery.
References
1.
Hofer S, Karaus A, Frahm J: Reconstruction and dissection of the entire human visual pathway using diffusion tensor MRI. Front Neuroanat
4:15, 2010
2.
Keles GE, Chang EF, Lamborn KR, Tihan T, Chang CJ, Chang SM, et al: Volumetric extent of resection and residual contrast enhancement on
initial surgery as predictors of outcome in adult patients with hemispheric anaplastic astrocytoma. J Neurosurg 105:34-40, 2006
3.
Klein J, Erhard P, Hahn HK: Resolution-Dependent Differences in Fiber Tracking and Quantification of the Visual Pathways, in Joint Annual
Meeting ISMRM-ESMRMB. Stockholm, Sweden, 2010, p 1660
4.
Pope WB, Sayre J, Perlina A, Villablanca JP, Mischel PS, Cloughesy TF: MR imaging correlates of survival in patients with high-grade gliomas.
AJNR Am J Neuroradiol 26:2466-2474, 2005
5.
Stieglitz LH, Lüdemann WO, Giordano M, Raabe A, Fahlbusch R, Samii M: Optic radiation fiber tracking using anteriorly angulated diffusion
tensor imaging: A tested algorithm for quick application. Neurosurgery, 2011
25
Proteomic Identification of target molecules as prognostic and therapeutic
marker in human gliomas using a new brain tumor bank
Jörg W. Bartsch1, Uwe Schlomann1, Susanne Schieber1, Catharina Conrad1, Fangyong Dong1,
Barbara Carl1, Axel Pagenstecher2, Christopher Nimsky1.
1
2
Klinik für Neurochirurgie und Abteilung für Neuropathologie, Philipps-Universität Marburg, Baldingerstr.,
35033 Marburg
With our current research, we aim to identify novel markers of human gliomas using a proteomic approach. As an example, we and others have characterised a metalloprotease activity, ADAM8, as a marker of poor prognosis and low survival rates in human gliomas. We
explored the functional role of ADAM8 in gliomas by generating U87 glioma cell lines by
knockdown of ADAM8 that caused a significant reduction in migration and invasion behaviour of U87 cells. As a result of ADAM8 knockdown, proteolytic release of a number of
membrane proteins was markedly reduced, including CD44, JAM-B and osteopontin, molecules with essential functions in glioma cell migration, i.e. accounting for metastasis and
infiltration of glioma cells. In addition, other members of the ADAM gene family are involved in growth, invasion and metastasis of glioma cells. We plan to combine all of these
findings to validate ADAM proteases as potential markers in biological samples from glioma
patients. To achieve this, we will make use of materials from a tumor bank that will be established in the near future. With such specimens, we will be able to employ state-of the art
techniques such as PrAMA (proteolytic activity matrix assays), allowing us to assess a “proteolytic footprint” of human gliomas. The goal of this study is to compare relevant activities
between glioma and healthy control samples in body fluids such as serum and urine in order
to identify novel markers for prognosis and therapy efficiency, i.e. for monitoring TMZ (Temodal®) efficacy.
26
Andreas Becker1, Jana Brüßler2, Daniela Kuhnt1, Elena Marxer2, Udo Bakowsky2,
Christopher Nimsky1
1
University of Marburg, Department of Neurosurgery, 35033 Marburg, Germany
University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, 35037 Marburg,
Germany
2
Introduction
The ultrasonic contrast properties of nanoscaled ultrasound contrast agents DPPC-PEG-40stearate, DSPC-PEG-40-stearate and DPPC-CHOL compared to the commercial available SonoVue® are reported in this study. Ultrasound contrast enhanced imaging is widely used in
diagnostic ultrasound to increase the power of backscattered signal and reduce the signalto-noise ratio [1]. Linear and non-linear properties and therefore generating of harmonics
of encapsulated microbubbles are responsible for this behavior.
Methods
Phased inversion harmonic imaging [2] of a medical ultrasound device equipped with a 2.5
MHz phased array transducer was used to measure the second harmonics of the samples in
a flow model during 60 seconds of insonation at 1.4 MHz with a mechanical index of 0.4.
Box counting lacunarity Fλ and box counting fractal dimension DB were used to describe
homogeneity and texture of contrast enhancement. Ultrasound images of 8, 10, 12, 16, 30
and 60 seconds after administration were stored in DICOM-format and digitally preprocessed to obtain binary images, where white spots on a black background indicate contrast
enhancement. The slopes of lacunarity were used for statistics. Low slope values indicate
homogeneity of digital images.
Results
Lowest slope values were obtained from DPPC-PEG-40-stearate. We found significant lower
λ values compared to SonoVue® p(<0.01) for the first 30 seconds of insonation. We found
no significant differences in lacunarity within the DPPC-PEG-40-stearate time-serie for images 10, 12, 30 and 60 seconds after administration (p=0.95) whereas the image of 16
seconds showed the lowest λ in this study.
Conclusion
We assume a loss of shell stability during insonation for DPPC-CHOL and DSPC-PEG-40stearate and high values of compressibility and therefore stability for DPPC-PEG-40-stearate
and SonoVue® [3]. The higher density of nanoscaled liposomes compared to SonoVue®
within a given volume results in an increasing homogeneity of images and therefore a higher value for backscattering coefficient. Homogeneity is a crucial diagnostic value in US diagnostic, e. g. in perfusion imaging of tumor or inflammation as well as in diagnostic of stroke.
Further studies of a new promising nanoscaled contrast agent DPPC-PEG-40-stearate are
necessary to obtain physicochemical properties.
References:
[1] E. C. Unger, T. Porter, W. Culp, R. Labell, T. Matsunaga, R. Zutshi, Therapeutic applications of lipid-coated microbubbles., Adv Drug Deliv Rev 56 (9) (2004)
1291–1314. doi:10.1016/j.addr.2003.12.006.
[2] D. H. Simpson, C. T. Chin, P. N. Burns, Pulse inversion doppler: a new method for detecting nonlinear echoes from microbubble contrast agents, IEEE Trans
Ultrason Ferroelectr Freq Control 46 (2) (1999) 372–82. doi:10.1109/58.753026.
[3 N. de Jong, R. Cornet, C. Lanc ee, Higher harmonics of vibrating gas-filled microspheres. part one: Simulations, Ultrasonics
32 (6) (1994) 447–453.
27
Andreas Becker1, Elena Marxer2, Jana Brüßler2, Udo Bakowsky2, Christopher Nimsky1
1
University of Marburg, Department of Neurosurgery, 35033 Marburg, Germany
University of Marburg, Department of Pharmaceutical Technology and Biopharmaceutics, 35037 Marburg,
Germany
2
Introduction
Ultrasound contrast enhanced imaging is widely used in diagnostic and therapeutic ultrasound to reduce the signal-to-noise ratio [1]. Non-linear oscillation and therefore generating of integer harmonics of the fundamental frequency is responsible for this behavior. The
aim of our study was to examine the contrast properties of ideally nanosized 100nm to
300nm liposomes made of dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and polyethyleneglycol-40stearate (PEG-40-STEA) compared to the commercial available SonoVue™ .
Methods
A medical ultrasound device (Siemens, SonoLine Elegra) equipped with a 2.5 MHz phased
array transducer was used to measure the second harmonics of the samples in a flow model
[2, 3]. Fundamental frequency was 1.4 MHz with a mechanical index (MI) of 0.4. Ultrasound
images of 8, 10, 12, 16, 30 and 60 seconds after administration were stored in DICOMformat. Images were digitally preprocessed to obtain binary images, where white spots on
a black background indicate contrast enhancement. For further calculation, a variable  was
computed as box-size divided by image-size. To find the pixel distribution, the number of
pixels in each -sized box was counted. Lacunarity λ for each grid of calibre  is calculated
from the standard deviation, σ, and mean, μ, for pixels per box. The slopes of λ were used
for statistics. Low slope values indicate homogeneity of digital images. A single factor analysis of variance was used to compare lacunarity.
Results
Lowest slope values were obtained from DPPC-PEG-40-STEA. We found significant lower
values λ compared to SonoVue™ p(< 0.01) for the first 30 seconds of insonation. We found
no significant differences in lacunarity within the DPPC-PEG-40- STEA time-serie for images
10, 12, 30 and 60 seconds after administration (p = 0.95) whereas the image of 16 seconds
showed the lowest λ in this study. In contrast, values of λ for Sonovue™ showed a broad
spreading during the time-series. Highest values of lacunarity were obtained from DPPCCHOL followed by DSPC-PEG-40-STEA.
Conclusion
Our results could be explained by the modeling of the RPNNP-equation that was modified
by de Jong et al. for encapsulate bubbles [4]: The resonance frequency of a microbubble is
inversely proportional to the bubble radius and proportional to the shell stiffness. By using
PIHI in our study the ultrasound device receives the second harmonic of the incident ultrasound beam and therefore DPPC-PEG- 40-STEA bubbles oscillated near their resonance frequency. Because of the low variance in bubble size of DPPC-PEG-40-STEA the range around
the resonance was not as broad as in SonoVueTM and therefore, low values indicate homogeneity of ultrasound images. The nanoscaled DPPC-PEG-40 STEA could be a promising contrast agent in ultrasound diagnostic and therapeutics, e.g. diagnosis of vascularisation in
tumors, target drug delivery and functional ultrasound (perfusion measurement) in ischemic diseases like stroke or myocardial ischemia.
28
References:
[1] E. C. Unger, T. Porter, W. Culp, R. Labell, T. Matsunaga, R. Zutshi, Therapeutic applications of lipid-coated microbubbles., Adv Drug Deliv Rev 56 (9) (2004)
1291–1314.
[2] D. H. Simpson, C. T. Chin, P. N. Burns, Pulse inversion doppler: a new method for detecting nonlinear echoes from microbubble contrast agents, IEEE Trans
Ultrason Ferroelectr Freq Control 46 (2) (1999) 372–82.
[3] C. Kollmann, R. A. Bezemer, K. E. Fredfeldt, U. G. Schaarschmidt, C. J. Teirlinck, A test object for quality control of the
instrument for doppler (duplex) ultrasonography, based on the draft iec 61685 standard], Ultraschall Med 20 (6) (1999)
248–257.
[4] N. de Jong, R. Cornet, C. Lancee, Higher harmonics of vibrating gas-filled microspheres. part one: Simulations, Ultrasonics
32 (6) (1994) 447–453.
Patricia Garrido-Vásquez1, Marc D. Pell2, Silke Paulmann3, Bernhard Sehm4, and Sonja A.
Kotz4
1 University of Marburg, Faculty of Psychology, Department of General and Biological Psychology, Marburg,
Germany
2 McGill University, Montreal, Canada
3 University of Essex, Colchester, UK
4 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
We have previously shown that patients with Parkinson’s disease (PD) whose motor symptoms are dominant on the left side of the body exhibit early deficits in emotional prosody
processing (Garrido-Vásquez et al., submitted). These deficits become evident in the P200
component of the event-related potential (ERP), which is thought to reflect the detection of
emotional significance from prosodic cues. Interestingly, prosodic stimuli in pseudo-speech,
i.e., speech devoid of semantics, did not elicit processing differences in PD patients relative
to healthy controls. Therefore, the impairment may concern the binding between different
sources of affective information, i.e., prosody and semantics, rather than emotional prosody processing per se. In an attempt to verify and extend these findings, we assessed the
interaction of two nonverbal emotion channels (prosody and facial expressions) in PD by
means of a cross-modal priming paradigm. Results revealed that the ERP modulation by
cross-modal prime-target congruency occurs later in PD patients with dominant left-sided
motor symptoms than in healthy controls and PD patients whose motor symptoms are dominant at the right. These findings indicate that the interaction of different communicative
channels conveying emotional information is disturbed in left-dominant PD and underline
once more that PD does not constitute a unitary disease profile.
References
Garrido-Vásquez, P., Pell, M. D., Paulmann, S., Strecker, K., Schwarz, J., & Kotz, S. A. (submitted). Motor symptom asymmetry matters: new evidence on vocal emotion processing in Parkinson’s disease.
29
Mirjam Stratmann, Udo Dannlowski, Axel Krug, Tilo Kircher, Carsten Konrad
Department of Psychiatry, University of Marburg, Germany
Background
Major depressive disorder (MDD) is a serious psychiatric disorder with a variety of structural brain
abnormalities being reported. In the current study, voxel-based morphometry was used to investigate gray matter volume differences between patients with unipolar major depression and healthy
controls. The primary aim of the study was to characterize and quantify gray matter reductions in
patients with MDD. A second goal was to analyse and quantify the influence of number of depressive episodes on gray matter volume.
Methods
In this structural magnetic resonance imaging (MRI) study, 132 patients with MDD (mean age
37.86+11.87 years; 76 female, 56 male) and 132 sex- and age-matched healthy control participants
(mean age 37.82+11.42 years; 74 female, 58 male) were included. To analyse gray matter abnormalities in patients with MDD, imaging data were analysed using voxel-based morphometry technique. We performed whole-brain analyses as well as ROI-analyses (hippocampus, ACC, amygdala
and insula).
Results
Compared to healthy control participants, patients with MDD showed significant gray matter reduction in the right insula lobe. In addition, ROI analyses revealed significant gray matter reductions
parahippocampal in the left hemisphere. There were no differences in regional gray matter volume
between controls and patients with first depressive episode. In contrast, patients with recurrent
depressive episodes showed significant gray matter reductions in the right superior temporal gyrus
and the right insula lobe. Number of depressive episodes was negatively correlated with gray matter
volume in the right insula lobe, left middle temporal gyrus, left superior temporal gyrus and left
inferior parietal lobe.
Conclusions
The most significant gray matter reductions in patients with MDD were identified in the right insula
lobe. Furthermore we found a negative correlation between number of episodes and gray matter
volume of the right insula lobe. In consideration of functional and structural imaging studies, there is
accumulating evidence that the insula cortex might be an important structure involved in MDD. Our
findings suggest that gray matter reduction of the insular cortex in patients with MDD is caused by a
recurrent course of illness
30
Neural correlates of physical and social causality in patients with schizophrenia and healthy controls: Preliminary results
Kim C. Wende1, Arne Nagels1, Mirjam Stratmann1, Anjan Chatterjee2, Tilo Kircher1, Benjamin Straube1
1 Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, D-35039
Marburg, Germany
2 Department of Neurology and the Center for Cognitive Neuroscience, The University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
The perception of cause and effect is fundamental to human cognition, allowing us to predict and operate with the world around us. Humans have the impression of one object causing the other to move even in displays of simple two-dimensional shapes, e.g. one billardlike ball seeming to collide with and push another (launching event, [1]). Perceived social
causality refers to the impression of a social interaction of moving objects/shapes in animated videos and the attribution of personality traits on these objects. Previous studies
indicate that, dependent on specific symptoms within schizophrenia spectrum disorder,
patients show an altered perception of causality in comparison to healthy controls [2]. The
aim of the present study is to identify the neural correlates of processing and interpretation
of physical and social causality in patients with schizophrenic patients and healthy control
subjects, respectively.
During fMRI-Data acquisition, healthy control subjects (n=18) and patients with schizophrenia (n=11) were presented with and asked to judge causal relationships (C) vs. movement
direction (D; control task) in two types of animated videos: A blue ball colliding with a red
ball (P; physical condition), and a blue ball passing the red ball without contact and then
straying off the track at a level with the red ball in various angles (S; social condition). The
stimulus-parameters angle and time delay were varied equally for both video types. The
subjects were instructed to ether judge the physical relationship (“Is the blue ball the cause
of the movement of the red ball?”) or the social relationship between both objects (“Is Mrs.
Red the cause of the movement of Mr. Blue?”). We contrasted each causality judgement
condition (PC, SC) with its control condition (direction judgement) using the same videos
31
(PD, SD).
In the control group we found for the judgement of both physical and social causality contrasted to judgement of movement direction (PC>PD ∩ SC>SD) activation of a frontoparietal network. First preliminary analyses of the patient data revealed a more bilateral
frontal activation pattern for the patient group compared to the control group. Healthy subjects showed a mainly left lateralized frontal activity. They also involved more parietal areas
during the judgement of physical and social causality than patients with schizophrenia.
These preliminary results might indicate that perception of causality in patients with schizophrenia is less dependent on parietal brain structures and requires more involvement of
frontal brain regions. These data suggest that perceptual cues processed within the parietal
lobe [3] are less relevant for patients with schizophrenia in contrast to healthy controls.
Further analyse will show if patients with schizophrenia have symptom specific alterations
in their judgement criteria, e.g. increased perceived causality associated with positive symptoms [2]. The objective of the prospective data analyses is to identify the neural base of the
expected symptom-specific differences.
Correspondence: Kim Wende, Department of Psychiatry and Psychotherapy, PhilippsUniversity Marburg, Rudolf-Bultmann-Str. 8, D-35039 Marburg, Germany, e-mail: [email protected], tel. ++49 (6421) 58-66932
References
[1] Wagemans, J., van Lier, R., and Scholl, B. J. (2006). Michotte’s heritage in perception and
cognition research. Acta. Psychol. 123, 1–19.
[2] Tschacher, W. & Kupper, Z. (2006). Perception of causality in schizophrenia spectrum
disorder. Schizophrenia Bulletin. 32. 106-112.
[3] Straube, B., & Chatterjee, A. (2010). Space and time in perceptual causality. Frontiers in
Human Neurosciences 4, 28. doi:10.3389/fnhum.2010.00028
32
Adipositasmarker in der Risikoevaluation von Subgruppen des Schlaganfalls
Yaroslav Winter1, Jakob Linseisen2 , Sabine Rohrmann2, Oliver Lanczik3, Peter A. Ringleb4,
Richard Dodel1, Wolfgang Oertel1, Johannes Hebebrand5 und Tobias Back6
1
Klinik für Neurologie, Philipps-Universität Marburg
Abteilung für Klinische Epidemiologie, Deutsches Krebsforschungszentrum, Heidelberg
3
Neurologische Klinik, Universitätsklinikum Mannheim, Universität Heidelberg
4
Neurologische Klinik, Universitätsklinikum Heidelberg, Universität Heidelberg
5
Klinik für Kinder- und Jugendpsychiatrie, Rheinische Kliniken Essen, Universität Duisburg-Essen
6
Neurologische Klinik, Sächsisches Krankenhaus Arnsdorf
2
Ziel: Die Adipositas ist ein unabhängiger Risikofaktor für vaskuläre Erkrankungen. Jedoch
wurde die Adipositas als Risikofaktor für Subgruppen der Schlaganfallerkrankung bisher
unzureichend untersucht. In der aktuellen Fallkontrollstudie wurden verschiedene
Adipositasmarker auf Assoziation mit Schlaganfallsubgruppen untersucht.
Methoden und Patienten: In die Fallkontrollstudie mit 1137 Teilnehmern (379 Fälle und 758
Kontrollen) wurden konsekutive Patienten mit den Diagnosen ischämischer Hirninfarkt (IH,
n=301), transitorisch ischämische Attacke (TIA, n=41) und intrazerebrale Blutung (ICB,
n=37) eingeschlossen. Für jeden Indexpatienten wurden zwei regionale Kontrollen ohne
zerebrovaskuläre Krankheit nach Alter und Geschlecht gematcht. Die Adipositasmarker
Bauch- und Hüftumfang, body mass index (BMI) und waist-to-hip ratio (WHR) wurden auf
Assoziation mit Schlaganfallsubgruppen untersucht. Die Statistik erfolgte mittels logistischer
Regressionsanalyse mit Adjustierung für vaskuläre Risikofaktoren (Hypertonie, Diabetes,
Rauchen, physische Inaktivität).
Ergebnisse: Es fand sich keine signifikante Assoziation zwischen BMI und dem Risiko für ICB
oder TIA. Patienten mit einem BMI >= 30 kg/m^2 hatten ein 2.9fach (95% CI 1,9-4,4) erhöhtes Risiko für IH (p<0,01). Nach Adjustierung für Risikofaktoren war diese Assoziation jedoch
nicht mehr signifikant. Ein Bauchumfang von >=102 cm (Männer) bzw. >=88 cm (Frauen)
war nach Adjustierung mit einer 4fachen Risikoerhöhung für IH oder TIA assoziiert (p<0,01).
Nach Adjustierung zeigte eine WHR von >=1,0 (Männer) bzw. >=0,85 (Frauen) ein 5,6fach
erhöhtes Risiko für IH (95% CI 3,8-8,3, p<0,01), ein 3,9fach erhöhtes Risiko für ICB (95% CI
1,7-8,6, p<0,01) und ein 2,8fach erhöhtes Risiko für TIA (1,3-6,0, p=0,01).
Zusammenfassung: Im Unterschied zum BMI konnten Marker der abdominalen Adipositas
(Bauchumfang, WHR) als unabhängige Risikoprädiktoren in allen evaluierten Subgruppen
der Schlaganfallerkrankung identifiziert werden. Demnach zeigt das abdominale Fettverteilungsmuster das höchste Risiko für die Subgruppe ischämischer Hirninfarkte.
Die Studie wurde im Rahmen von NGFN-2 vom BMBF gefördert.
33
Diffusion Tensor Imaging (DTI) in idiopathic REM sleep behaviour disorder
(iRBD)
Belke M.1, Unger M.M. 1, Hattemer K. 1, Heverhagen J.T. 2, Keil B. 2, Stiasny-Kolster K. 1,
Rosenow F. 1, Diederich N.J. 3, Mayer G. 4, Möller J.C. 1, Oertel W.H. 1, Knake S. 1
1Philipps Universität Marburg, Neurologie, Marburg
2Philipps-Universität Marburg, Department of Diagnostic Radiology, Marburg
3Centre Hospitalier de Luxembourg, Department of Neurosciences, Luxembourg
4Hephata-Clinic for Neurology, Schwalmstadt
Introduction:
Idiopathic REM sleep behaviour disorder (iRBD) - a parasomnia characterized by dream
enactments – is a risk factor for the development of Parkinson’s disease (PD) and other alpha-synucleinopathies. The pathophysiology of iRBD is likely due to dysfunction of brainstem
nuclei that regulate REM sleep.
Material and Methods:
Diffusion tensor imaging (DTI) of the brain is a method for studying the microstructural brain
tissue integrity in vivo. We investigated whether DTI detects microstructural abnormalities in
brains of patients with iRBD - compared with age-matched controls - as a potential in vivo
indicator for changes related to “preclinical (premotor)” PD neuropathology. Patients with
iRBD (n=12) and age-matched healthy controls (n=12) were studied using a routine 1.5T MRI
scanner. Whole-head DTI scans (measuring fractional anisotropy (FA), axial diffusivity (AD), a
potential marker of neuronal loss and radial diffusivity (RD), a potential marker of myelin
pathology) were analyzed without a priori hypothesis using tract-based spatial statistics
(TBSS), a novel technique minimizing edge-related artifacts and alignment difficulties.
Results:
Using group analysis, we found significant microstructural brain tissue changes (p < 0.0001)
in the white matter of the brainstem (AD), the olfactory region (FA), the left temporal lobe
(RD), the fornix (RD), the internal capsule (FA), the corona radiata (AD), the right visual
stream (RD) and the right substantia nigra (AD) of the iRBD patients.
Discussion:
These microstructural abnormalities were identified in regions known to either be involved
in REM-sleep regulation (brainstem) and/or to exhibit neurodegenerative pathology in iRBD
and/or early PD. The study suggests that iRBD-related microstructural abnormalities can be
detected in vivo with DTI, a widely available MRI technique.
34
How Stress gets in the Body – A Psychobiological Approach to the Pathophysiology of Chronic Fatigue
Strahler, J., Skoluda, N., Doerr, J.M., Nater, U.M.
Clinical Biopsychology, Philipps University of Marburg, Marburg, Germany
Severe chronic fatigue is characterized by generalized weakness causing an inability to perform certain activities, easy fatigability and decreased ability to maintain performance, and
mental fatigue associated with cognitive impairment and emotional lability. Stress has been
suggested as a potential pathophysiological factor of fatigue. Despite the wealth of data on
physiological alterations in stress systems in fatigued patients, only few consistent findings
can be summarized. There seems to be a relative hypoactivity of the hypothalamicpituitary-adrenal axis, increased autonomic nervous system activity, and increased immune
activity. However, we are far from a detailed understanding of the intricate relationship
between these stress systems and fatigue. Interestingly, some previous studies in patients
suffering from chronic fatigue have found gene expression alterations in individual genes or
biological pathways, which are known to be involved in the biological stress response. However, it is not known whether gene expression levels in individuals with chronic fatigue are
differentially up- or down-regulated in the context of chronic or acute stress.
This project focuses on the elucidation of the pathophysiology of chronic fatigue. We believe that people suffering from chronic stress exhibit increased stress reactivity and increased fatigue levels associated with differences in gene expression profiles. To this end,
caregivers of patients suffering from a severe disease (e.g., brain cancer or progressive dementia) will be examined and stratified into a fatigued and non-fatigued group. Caregiving is
well-established as valid model of chronic stress. Our project studies acute as well as chronic stress effects in fatigued and non-fatigued caregivers. The first goal of this project is to
study patterns of stress-responsive genes by exposing participants to a psychological stressor while implementing time-series sampling. The second goal is to examine possible associations between stress experiences in daily life and fluctuations on symptom manifestation
of fatigue. For this purpose, we will study fatigue levels and potential factors that may contribute to fatigue maintenance as they occur in the caregivers’ daily life environments, using
a 14-day ambulatory assessment method. Momentary assessment of stress experiences,
symptom manifestation, and concomitant physiological alterations will thus be measured in
a dynamic rather than static manner.
Our approach allows for adequate assessment of associations between molecular alterations, endophenotypes, and symptoms. This will enable us to depict complex interactions of
symptomatology and environmental context in people suffering from chronic fatigue.
35
Chavanon, M.-L., & Peper, M
Experimental and Physiological Psychology, Philipps-University of Marburg, Marburg, Germany
Several lines of evidence suggest that electrocortical posterior vs. anterior theta activity (4–
8 Hz) recorded during resting situations (i.e., in absence of a specific task) reflects endogenous cortical dynamics of rostral anterior cingulate (rACC) theta activity, agentic extraversion
(aE), and optimistic, positive mentalizing. Although posterior vs. anterior theta activity has
been consistently found to be associated with aE, information about the psychometric
properties of this measure is missing. The present study now fills this gap. We evaluated the
temporal stability of posterior vs. anterior theta and rACC in N = 40 male participants either
high or low in aE by recording resting EEG activity on two separate experimental occasions
4-5 weeks apart. First, for each session, participants scoring high on aE depicted less frontally distributed theta activity compared to low aE, replicating our earlier findings (e.g., Chavanon, Wacker, Stemmler, 2011). Second, resting posterior vs. anterior theta demonstrated
satisfactory test-retest stability (rs > .55) and excellent internal consistency reliability (Cronbach Alphas >.75) in both groups. Discussion focuses on the implications of the present
findings for the measurement and conceptualization of resting posterior vs. anterior theta
activity as a measure assessing individual differences in agentic, dopaminergically based
extraversion.
36
Trial-by-trial adjustments of control during selective long-term-memory retrieval are mediated by a fronto-parietal network
Jasmin M. Kızılırmak & Patrick H. Khader,
Philipps-University Marburg, Germany
We investigated neural processes controlling selective long-term-memory retrieval when
different associations with a cue have to be accessed consecutively by employing a paradigm that varied whether the cue, the to-be-retrieved association, or the number of to-beretrieved associations changed from trial to trial. We found trial-by-trial adjustments of retrieval control to be mediated by a fronto-parietal network: (1) Bilateral supramarginal gyri
(SMG, BA 40/39) and left middle frontal gyrus (MFG, BA 10) showed stronger activation
when a single association had to be retrieved after all associations with the same cue had
been accessed compared to having accessed only one other association previously. (2) The
same condition revealed activation of right inferior frontal gyrus (IFG, BA 46/45/44) and
bilateral, more anterior parietal regions (BA 40) compared to when the relevant associations in consecutive trials related to different cues. These results suggest that left MFG handles episodic interference from previously accessed associations, while SMG activation reflects increased demands to focus attention on a single association after all associations
with the cue had been active. Furthermore, right IFG and additional parietal regions seem
to be involved in controlling the specific interference arising from switching between relevant associations within one and the same cue-associations net.
37
Kontrolltransfer bei probabilistischen Entscheidungen: Beziehungen zu
Selbsteinschätzungen der Belohnungs und Bestrafungssensitivität
Martin Peper & Mira-Lynn Chavanon
Philipps-Universität Marburg,
Beim klassisch-instrumentellen Transferlernen (Pavlovian-to-Instrumental Transfer; PIT)
handelt es sich um ein tierexperimentell gut untersuchtes Paradigma zum Nachweis von
Wechselwirkungen assoziativer und instrumenteller Lernprozesse. Um PIT im Humanexperiment zu erkunden, wurde in dieser Untersuchung eine neue probabilistische Entscheidungsaufgabe eingesetzt und geprÃ¼ft, ob belohnende oder aversive konditionierte (auditive) Hinweisreize auf das annäherungsbezogene instrumentelle Verhalten eine
faszilitierende oder beeinträchtigende Wirkung haben. Da gemäß der Reinforcement
Sensitivity Theory (RST; Gray und McNaughton, 2000) die Verarbeitung appetitiver bzw.
aversiver Reize durch drei unterschiedliche neurobiologische Verhaltenssysteme vermittelt
wird, wurden die Verhaltensindikatoren des PIT mit den habituellen Sensitivitäten des
Behavioural Approach System (BAS) und des Behavioural Inhibition System (BIS) (mit den
Carver-White-BIS/BAS-Skalen erfasste Selbsteinschätzungen) in Beziehung gesetzt. Die Verhaltensdaten bestätigen verhaltenshemmende bzw. -fördernde Transfereffekte aufgrund
aversiver bzw. appetitiv konditionierter Hinweisreize. Erste differentiell-psychologische Befunde zu den BIS/BAS-Korrelaten auf Verhaltensebene werden fÃ¼r die unterschiedlichen
experimentellen Kontexte berichtet und im Rahmen der Reinforcement Sensitivity Theory
diskutiert. Talmi, D., Seymour, B., Dayan, P., & Dolan, R.J. (2008).Human pavlovianinstrumental transfer. Journal of Neuroscience, 28, 360-368.
Pecina, S., Schulkin, J., & Berridge, K.C. (2006). Nucleus accumbens corticotropin- releasing
factor increases cue-triggered motivation for sucrose reward: paradoxical positive incentive
effects in stress? BMC Biology, 4, 8.
Doya, K. (2008). Modulators of decision making. Nature Neuroscience, 11, 410â€“416.
38
Ultrasonic communication in rats: Effects of post-weaning social isolation on
social approach behavior and brain activity in response to playback of appetitive
D. SEFFER, C. RENNINGER, R.K.W. SCHWARTING, M. WÖHR
Rats emit distinct types of ultrasonic vocalizations (USVs), which serve as situationdependent affective signals. Juvenile and adult rats produce 50-kHz USVs in appetitive situations such as rough-and-tumble play, mating or when tickled playfully, whereas 22-kHz
USVs occur in aversive situations such as fear-conditioning or social defeat, probably reflecting positive and negative affective states, respectively. In support of a communicative function of USVs, it was demonstrated that 50-kHz USVs and 22-kHz USVs induce call-specific
behavioral responses in the receiver. 50-kHz USVs induce social approach behavior, supporting the notion that they serve as social contact calls. In contrast, 22-kHz USVs leads to
freezing behavior, indicating an alarming function (Wöhr & Schwarting, PLoS One, 2007).
The opposite behavioral responses are paralleled by distinct patterns of brain activation.
While 22-kHz USVs induce activation in amygdala and periaqueductal gray, 50-kHz USVs are
followed by activation in the nucleus accumbens (Sadananda et al., Neuroscience Letters,
2008). Since rats are social animals and rough-and-tumble play during adolescence has an
important role for social development, separation from conspecifics during this phase is
known to impair social behavior.
Here, we tested whether post-weaning social isolation impairs social approach behavior in
response to playback of 50-kHz USVs. Rat weanlings were housed under one of the following three conditions: group housing, short-term isolation, i.e. 24 hours, or long-term isolation, i.e. 28 days. Then, they were tested for social approach behavior in response to 50-kHz
USVs. As acoustic control stimuli served 22-kHz USVs and background noise. We applied cfos immunocytochemistry to screen for playback-induced neuronal activation in brain areas
implicated in the regulation of affect and social behavior.
Confirming previous findings, playback of 50-kHz and 22-kHz USVs elicited opposite behavioral responses and distinct neuronal activation patterns. Post-weaning social isolation specifically affected the behavioral response to 50-kHz USVs. Group housed rats showed a clear
preference towards 50-kHz USVs. Socially deprived short-term isolated rats exhibited an
even stronger reaction, possibly due to a higher level of social motivation. In contrast, no
social approach behavior was observed in long-term isolated rats, highlighting the importance of social experience during adolescence for affiliative behavior.
39
Liste der aktiven Teilnehmer/innen (alphabetische Reihenfolge)
A. Becker, J. Brüßler, D. Kuhnt, E. Marxer, U. Bakowsky, C. Nimsky
S. Oppermann, K. Elsaesser, C. Krasel, J. Grohm, F. Schrader, S. Glinca, M. Bünemann, G. Klebe, M. Schlitzer, C. Culmsee
P. Garrido-Vásquez, M. D. Pell, S. Paulmann, B. Sehm, S. A. Kotz
Enhanced Performance in a sequential reaction time task in a rat model of temporal
lobe epilepsy with classic hippocampal sclerosis
B. Norwood, M. T. Eckart, J. Will, R. Schwarting, F. Rosenow
Extracellular long-term recordings from polarization-sensitive interneurons of the locust brain
M. Bech, U. Homberg
From the antenna to the mushroom body: The olfactory pathway of the red flour
beetle Tribolium castaneum
M. Kollmann, S. Dippel , S. Frank, M. Binzer, C. Heuer, S. Schütz, E. A. Wimmer, J.
Schachtner
A. Becker, E. Marxer, J. Brüßler, U. Bakowsky, C. Nimsky
How Stress gets in the Body – A Psychobiological Approach to the Pathophysiology of
Chronic Fatigue
J. Strahler, N. Skoluda, J. M. Doerr, U. M. Nater
Kontrolltransfer bei probabilistischen Entscheidungen: Beziehungen zu Selbsteinschätzungen der Belohnungs und Bestrafungssensitivität M. Peper, M.-L. Chavanon
Loss of IRF9 Prevents Lethal Lymphocytic Choriomeningitis Virus Infection in Mice at
the Cost of Viral Persistence and Chronic Inflammation in the CNS
M. J. Hofer, C. Koehler, W. Li, P. Manders, I. L. Campbell
Membrane-type matrix metalloproteinases differentially promote the migration and
invasion of murine astrocytes in various in vitro assays
R. Merten, A. Voß, A. Schmidt, J.W. Bartsch, A.Pagenstecher
40
Modulation of adult neurogenesis in the olfactory bulb in an acute mouse model of
Parkinson’s disease
W.-H. Chiu, T. Carlsson, M. Arend, G. Höglinger, W. H. Oertel, V. Ries
Morphology of two parallel visual pathways through the anterior optic tubercle of the
bumblebee
K. Pfeiffer and M. Kinoshita
M. Stratmann, U. Dannlowski, A. Krug, T. Kircher, C. Konrad
Neural correlates of physical and social causality in patients with schizophrenia and
healthy controls: Preliminary results
K.C. Wende, A. Nagels, M. Stratmann, A. Chatterjee, T. Kircher, B. Straube
M. Binzer, C. M. Heuer, J. Schachtner
C. M. Heuer, M. Binzer, J. Schachtner
M. H. A. Bauer, D. Kuhnt, D. Freitag, C. Nimsky
Pharmacological modulation of KCa2 channels as therapeutic strategies for neurodegenerative disorders
M. Dolga, R. Dodel, G. Höglinger, N. Plesnila, C. Culmsee
Post Metamorphic Plasticity of Numbers of Peptidergic Neurons in the Antennal Lobe
of Tribolium castaneum
Proteomic Identification of target molecules as prognostic and therapeutic marker in
human gliomas using a new brain tumor bank
J. W. Bartsch, U. Schlomann, S. Schieber, C. Conrad, F. Dong, B. Carl, A. Pagenstecher, C.
Nimsky
Quantitative Analysis of the Neuropeptide Concentration in the Antennal Lobes of
Aedes aegypti
A. Reifenrath, K.P. Siju, C. Wegener, S. Neupert, J. Kahnt, B.S. Hansson, F. Hauser, R.
Predel, R. Ignell, J. Schachtner
Reduced tumor load and metastasis in vivo by targeting a metalloprotease-disintegrin,
ADAM8, in highly invasive adenocarcinomas
U. Schlomann, T. Ferdous, P. Golfi, G. Koller, T. Hagemann, M. Bossard, C. Nimsky, J.W.
Bartsch
Responses of central-complex neurons oft he locust to expanding shapes
41
R. Rosner, U. Homberg
M.-L. Chavanon, M. Peper
Schädigungsmechanismen in Mitochondrien als neue therapeutische Ansatzpunkte der
Neuroprotektion
Small molecule Bid inhibitors prevent Drp1-dependent mitochondrial fission and cell
death in neurons
S. Oppermann, J. Grohm, F. Schrader, C. Krasel, M. Bünemann, G. Klebe, M. Schlitzer, N.
Plesnila, C. Culmsee
Three dimensional reconstruction of neuropils and neurons in the central complex of
the desert locust, Schistocera gregaria
T. Bockhorst, R. Heidasch, J. Von Hadln, U. Homberg
Trial-by-trial adjustments of control during selective long-term-memory retrieval are
mediated by a fronto-parietal network
J. M. Kızılırmak, P. H. Khader
Ultrasonic communication in rats: Effects of post-weaning social isolation on social approach behavior and brain activity in response to playback of appetitive
D. Seffer, C. Renninger, R.K.W. Schwarting, M. Wöhr
42
Bitte schicken Sie diesen Antrag per Hauspost oder Fax unterschrieben an:
Philipps-Universität Marburg
Graduiertenzentrum Lebens- und Naturwissenschaften
z. Hd. Dr. Ute Kämper
Hans Meerwein Str. (Raum 07C01)
35032 Marburg
Fax: 06421 – 282 1398
Antrag auf Mitgliedschaft im Graduiertenzentrum Lebens- und
Naturwissenschaften der Philipps-Universität Marburg
- für betreuende Mitglieder –
_______________________________________________________________________________
Name, Vorname Fachbereich
_______________________________________________________________________________
Email-Adresse Institut
Institutsadresse
________________________________________________________________________________
Angabe des strukturierten Promotionsprogramms (falls zutreffend)
Als betreuendes Mitglied des Graduiertenzentrums werde ich der Sektion (bitte ankreuzen)
O Evolution, Biodiversität und Umwelt
O Experimentelle, klinische und kognitive Neurowissenschaften
O Quantifizierung und Strukturierung von Komplexität
O Molekulare und systemische Biowissenschaften
O Struktur- und Funktionsmaterialien
angehören.
Ich betreue im Fachbereich _____________________________________________
Promotionen und beantrage hiermit gemäß §4 Abs. 1b der Satzung des
Graduiertenzentrums die Mitgliedschaft im Graduiertenzentrum Lebens- und
Naturwissenschaften der Philipps-Universität. Ich erkläre meine Bereitschaft, die in der
Satzung des Graduiertenzentrums genannten Aufgaben betreuender Mitglieder (§ 5) zu
erfüllen.
Als Mitglied des Graduiertenzentrums Lebens- und Naturwissenschaften erkläre ich mich
damit einverstanden, dass mein Name auf der Internetseite des Zentrums veröffentlicht wird.
Als Mitglied erhalte ich automatisch den Newsletter, wenn ich keine gegenteilige Mitteilung
mache.
___________________________ _________________________
Marburg, den
Unterschrift
43
Antrag auf Mitgliedschaft im Graduiertenzentrum Lebens- und Naturwissenschaften als
promovierendes Mitglied
Application for membership in the Graduate Center Life and Natural Sciences
Ich beantrage die Mitgliedschaft im Graduiertenzentrum Lebens- und Naturwissenschaften
der Philipps-Universität Marburg und die Aufnahme in die Sektion
I apply for membership in the Graduate Center Life and Natuaral Sciences of the PhilippsUniversität Marburg and its scientific section
Die mit * gekennzeichneten Felder sind Pflichtfelder und müssen ausgefüllt werden.
All fields marked with an * are obligatory and must be filled in. 1. Anrede/Title:
Vorname / First Name:*
/Last Name:*
Strasse / Street:
Name
2.Anschrift (privat) / private Address:
*
PLZ, Ort / Postal Code, City:*
Telefon / Telephone:*
Fax:
mobil / cellular phone:
E-Mail:*
3.Mit welchem Abschluß haben Sie Ihr Studium beendet?
Please list the most recent degree you have earned:*
Bei Auswahl "sonstiger" bitte Bezeichnug des Abschlusses eintragen.
If you select "other", please include the name of the degree in the blank to the right. Welche
Fächer haben Sie studiert? / Please list your major(s) and/or area(s) of concentration *
1.
2.
3.
4.
Datum des Studienabschlusses / Date of Graduation:
jekts (Arbeitstitel der Dissertation):
Topic of Doctoral Project ( Working Title of Dissertation):*
4.Thema des Promotionspro-
Stichworte zum Promotionsprojekt
/ Keywords of your Doctoral Project:
1.
2.
3.
44
4.
5.
5.Betreuer/Betreuerinnen / Advisor(s):*
Titel/Title Vorname/First Name
Name/Last Name
Hochschule/Institution
1.
2.
3.
(Bei externen Betreuern bitte die Hochschule nennen.)
(For external advisors, please list the name of the institution.)
Angemeldet am / Date of registration:
te/Department:
6.Institut/Fachgebiet/Arbeitsgruppe / Institu-
*
7.Fachbereich / Faculty:*
8.Sind Sie an der Uni-
versität Marburg als Promotionsstudent/in immatrikuliert?
Are you already registered as a graduate student at the Philipps-Universität Marburg?
Ja/yes /
Nein/No 9.Welchen Mitarbeiterstatus haben Sie / wie werden Sie finanziert?
What type of position do you have at the university? / How do you finance your living expenses?
Wissenschafliche/r Mitarbeiter/in - 100 % Unimittel /"Wissenschaftliche/r Mitarbeiter/in" - 100% university funding
Wissenschafliche/r Mitarbeiter/in - 50 % Unimittel /"Wissenschaftliche/r Mitarbeiter/in" - 50% university
funding
Wissenschafliche/r Mitarbeiter/in - 50 % Drittmittel /"Wissenschaftliche/r Mitarbeiter/in" employee - 50%
external funding
Stipendium / grant
sonstige / other
(bei Auswahl sonstige bitte genaue Bezeichnung angeben)
If you select "other", please include detailed information in the blank to the right.
10.Haben Sie einen Schreibtisch/Arbeitsplatz an der Uni?
Do you have a desk/an office/ a workspace at the university?
chem Institut / If yes, in which institute/department?:
Ja/yes /
Nein/no 11.Wenn ja: an wel-
Institutsadresse / Address of institute/department:
Strasse / Street:
PLZ, Ort / Postal Code, City:
12.Sind Sie in die Lehre eingebunden (z.B. als wiss. Mitarbeiter/in oder Lehrbeauftragte/r)?
Wenn ja, mit welchem ungefähren Zeitaufwand (Angabe in SWS)?
Are you employed in a teaching capacity at the university (e.g., as a Teaching Assistant,
"Wissenschaftlicher Mitarbeiter" or "Lehrbeauftragter")? If yes, for how many hours per
45
week?
Haben Sie sonstige regelmäßige Aufgaben (außerhalb Ihres Dissertationsprojekts)?
Do you have other regular duties (other than those concerning your dissertation project)?
Wenn ja, mit welchem ungefähren Zeitaufwand (Angabe bitte in SWS) und in welchem Aufgabenfeld.
If yes, how many hours per week and in which area of responsibility?
13.Kurzbeschreibung des Dissertationsprojekts (max. eine Seite, d.h. 4000 Zeichen incl. Leerzeichen) mit Informationen zu Thema, Fragestellung, Materialbasis/Ansatz/Methoden und
Stand der Arbeit
Summary of the Dissertation Project (max. one page, ca. 4000 characters including spaces)
with information regarding the topic, questions to be discussed, materials/implementation/methods, and the current status of the project.
14.Mich interessiert vor allem...*
(Bitte stichwortartig aufführen, zu welchen Themen, theoretischen Grundlagen, Methoden,
Techniken etc. Sie Informationsbedarf haben):
I am primarily interested in...
Please list key words and phrases regarding topics, theoretical principles, methods, techniques, etc., about which you would like more information:
15.Ich selbst kenne mich gut mit
46
folgenden Themen aus (Stichworte):
I am personally well-acquainted with the following topics and could incorporate them into
work groups at the Graduate Center (key words):*
16.Ich kenne mich gut mit folgenden Arbeitstechniken und/oder Weiterbildungsmöglichkeiten (auch außeruniversitären) aus:
I am well-acquainted with the following work-, research- and/or vocational training techniques (including opportunities outside of the university):*
17.Ich bin bereits in ein Netzwerk
integriert (Promotionsprogramm wie z.B. Graduiertenkolleg, Graduiertenschule, SFB, Transregio, andere Institutionen, etc.):
I am already integrated into a system of networking (e.g., doctoral programms like "Graduiertenkolleg", Graduate School, SFB, Transregio, others):
18.An fächerübergreifenden Weiterbildungen interessieren mich insbesondere folgende Inhalte:
I am primarily interested in the following interdisciplinary vocational training techniques:
19.Sonstige Wünsche oder Bemerkungen:
Other requests or comments:
Ich abonniere den Newsletter:
I would like to subscribe to the newsletter: *
ja/yes /
nein/no
Als Mitglied des Grauiertenzentrums Lebens- und Naturwissenschaften erkläre ich mich damit einverstanden, dass mein Name auf den Internetseiten des Graduiertenzentrums veröffentlicht wird. Inhalt und Umfang der öffentlich zugängigen Daten lege ich selber fest.
As a member of the Graduate Center Life and Natural Sciences, I understand that my name
47
will be published on the Graduate Center's website. I can later determine the content of and
extend to which my project description appears online.
48

motivation - Philipps-Universität Marburg

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