Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

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172 gene EGFP under control of the c-kit promoter, for the direct identification of living ICC in situ and in culture. Creation of a core facility for laser microdissection and laser pressure catapulting (PALM system). Evaluation of the system and preliminary experiments have been performed in other Universities. The system will be used in our research program to validate candidates identified by the substractive technique described above. IV Involvement of the phosphoinositides cascade in the neural stem cells proliferation and differentiation The germinative ventricular zone (VZ) of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The ability to generate neurons persists at adulthood in restricted brain areas. During development, many growth factors exert their effects by interacting with tyrosine kinase receptors and activate the phosphatidylinositol-3 kinase and the Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently identified inositol polyphosphate 5-phosphatase 2 (SHIP2) has the potential to regulate neuronal development. Using in situ hybridization, we showed that SHIP2 mRNA was highly expressed in the VZ of brain and spinal cord and whereas no significant expression was seen differentiated fields [8]. This restricted expression was maintained from E12 to birth. In the adult brain, SHIP2 was mainly restricted in structures containing neural stem cells such as the anterior SVZ, the rostral migratory stream and the olfactory tubercle. The specificity of SHIP2 expression in neural stem cells was further demonstrated in the adult by the dramatic increase in SHIP2 signal in N-CAM-deficient mice, which present an accumulation of progenitor cells in the anterior SVZ and the rostral migratory stream. In collaboration with Dr. B. Rogister from the Center for Cellular and Molecular Neurobiology, University of Liege, the expression of the SHIP2 protein was assessed using Western blot analysis on neurosphere cultures either in proliferation or differentiation conditions. It was abundantly expressed in proliferating neurospheres whereas it was barely detectable in differentiated neurospheres, confirming therefore the specific expression in undifferentiated neural stem cells. The correlation between the pattern of SHIP2 expression in the brain and the proliferative and early differentiative events suggests that the phosphatase SHIP2 may have important roles in neural development. Experiments are now started in order to address the physiological relevance of this specific expression in the neural cell proliferation and/or differentiation process. V. 5-HT1A receptors in the KA model of limbic epilepsy in the rat In collaboration with the PET/Biomedical Cyclotron Unit (ULB), the correlation between hippocampal neuronal loss and in vivo 5-HT1A receptors detection as been assessed in the kainic acid (KA) model of limbic epilepsy in the rat [12]. A high density of 5-HT1A receptors is present in pyramidal hippocampal cells and they can be mapped in vivo using 18F-MPPF. We tested the hypothesis of a correlation between MPPF binding and post-epileptic neuronal loss in the hippocampus. Determination of MPPF binding in the brain was combined with a quantification of neuronal loss using DNA labeling with propidium iodide and confocal microscopy in brains of rats sacrificed 1 hour to 240 days after KA injection. An initial relative decrease in hippocampal MPPF binding from the 1 st to 6 th days was followed by an increase between the 6 th and 30 th days. This effect was observed in rats who showed hippocampal neuronal loss as well as
in those who did not. In rats sacrificed outside this initial period of time, correlation between hippocampal MPPF binding and neuronal loss was statistically significant. The increase of MPPF binding observed from the second week after KA injection suggests an unexpected epilepsyinduced increase of 5-HT1A receptors in the hippocampus. VI. Axonal transport of potassium channels The recent cloning, functional expression and brain localisation of two new potassium channels TREK and TRAAK led us to examine whether both channels are present in peripheral nerves and can move along axons by means of axonal transport mechanisms. Using specific antibodies directed against TREK and TRAAK peptides, we found that immunoreactivity for both potassium channels accumulates above and below a ligature in rat sciatic nerves [1]. The process was rapid and bi-directional indicating that the channels are associated with vesicles. VII. CCR5 chemokine receptor trafficking Study of receptor internalisation and trafficking kinetics in living cells expressing a recombinant CCR5 chemokine receptor tagged with EGFP (enhanced green fluorescent protein) and various of its mutants, by means of time-lapse confocal microscopy and FRAP (fluorescence recovery after photobleaching), respectively; in collaboration with Dr Cedric Blanpain and Prof. Marc Parmentier, Brussels (B). Publications 2000 Articles • BEARZATTO B., LESAGE F., REYES R., LAZDUNSKI M., LADURON P.M.: Axonal transport of TREK and TRAAK potassium channels in rat sciatic nerves. NeuroReport, 11: 927-930, 2000. (2,591). • DASSESSE D., LEDENT C., MEUNIER J.-C., PARMENTIER M. and SCHIFFMANN S.N.: Regulation of nociceptin mRNA expression in the septum by dopamine and adenosine systems, Neuroreport, 11:3243-3246, 2000 • CHERON G., SCHURMANS S., LOHOF A., d'ALCANTARA P., MEYER M., DRAYE J.-P., PAR- MENTIER M., SCHIFFMANN S.N.: Electrophysiological behavior of Purkinje cells and motor coordination in calretinin knock-out mice. Prog. Brain Res., 124 : 299-308, 2000. (1,950). •DE LAET M.-H., DASSONVILLE M., VAN DEN EIJNDEN S., LERMINIAUX C., SEGHERS V., BLUM D., VANDERWINDEN J.-M. : Small bowel perforation in very low birth weight neonates treated with high dose Dexamethasone. Eur. J. Ped. Surg., in press, 2000. •ISOZAKI K., TERRIS B., BELGHITI J., SCHIFFMANN S.N., HIROTA S., VANDERWINDEN J.- M.: Germ-line activating mutation in the kinase domain of c-kit gene in familial gastrointestinal stromal tumors. Am. J. Pathology, 157(5):1581-1585, 2000. (6,043). •VANDERWINDEN J.-M., RUMESSEN J.J., BERNEX F., SCHIFFMANN S.N., PANTHIER J.-J.: Distribution and ultrastructure of interstitial cells of Cajal in the mouse colon, using an antibodies to Kit and Kit W-lacZ mice. Cell Tissue Res., in press, 2000. (2,084). •VANDERWINDEN J.-M., RUMESSEN J.J., DE LAET M.-H., VANDERHAEGHEN J.-J., SCHIFF- MANN S.N.: CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract. Cell Tissue Res., in press, 2000. (2,084). 173
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Geneeskundige Stichting Koningin El
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Fondation Médicale Reine Elisabeth
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L’abondance et la qualité des pu
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Prof. Dr. A. Bossuyt Secrétaire du
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Prof. Dr. G. Orban Lab. voor Neuro-
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Reports of the University Research
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14 Members of the team: Christophe
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16 domains, most notably that of N-
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Report of the Research Group of Pro
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Part 1: Characterisation of noradre
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Part 2 : Chromogranins as neuro-imm
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Publications 2000 : • J. Depreite
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28 Collaborations with: A. Volny-Lu
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30 MATERIALS AND METHODS Surgery an
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32 RESULTS Recordings were obtained
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34 Responses to brush stimuli The s
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36 DISCUSSION This experimental stu
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PART 1: Molecular Pharmacology of A
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c) Most insurmountable AT 1 recepto
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dy tested biphenyl-tetrazole derive
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ii) More distant functional respons
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References •Aiyar N, Baker E, Vic
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•Olins GM, Chen ST, McMahon EG, P
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PART 2: The use of Endothelin 1 in
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vasoconstriction, peaked 20 minutes
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ACCEPTED • Vanderheyden P.M.L., F
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60 Prof. Dr. Christophe Erneux I.R.
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62 tion forming Ins(1,3,4,5)P 4 and
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64 Bibliography •Berridge, M.J. a
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68 University of Mons-Hainaut Labor
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70 Works carried out in 2000 1. We
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Genetic definition of brain tumours
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Analysing this way these 48 tumours
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Genetic determinants of mouse brain
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Genomic organization of the Dab1 ge
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In vitro studies of the hypothalami
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vitro GnRH release by intact male g
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Study on the functional regulation
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Elucidation of the DAT primary sequ
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The role of presenilin-1 in the gam
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INTRODUCTION As usual, this activit
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The acquisitions for this study sho
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not lead to the integrative process
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REFERENCES Thesis •Steven Laureys
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• Positron emission tomography in
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Before scanning, subjects practised
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RESEARCH PROGRAM ON MEMORY FUNCTION
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Page 141 and 142: •Identification of PSF, the PTB-a
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Page 147 and 148: Brain activations in a dot pattern
Page 149 and 150: References •R Vogels, G Sary, P D
Page 153 and 154: A Scientific activities 1. Overview
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Page 161 and 162: •Ledent C, Valverde O, Cossu G, P
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Page 167 and 168: I. Physiology and physiopathology o
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Page 187 and 188: I. FMRI in Awake Behaving Macaques
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Page 193 and 194: Future Possibilities Future contras
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Page 217 and 218: BIBLIOGRAPHY - 2000 Publications in
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1. Coding of 3D-shape in macaque in
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3. Position sensitivity of macaque
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Publications: •JANSSEN P., VOGELS
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Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

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