Geneeskundige Stichting Koningin Elisabeth ... - GSKE - FMRE

Functional significance of neuroreceptors on neural stem cells
Nguyen, L., Rocher, V., Belachew, S., Malgrange, B., Rogister, B., Moonen, G. and Rigo, J.M.
Centre de Neurobiologie Cellulaire et Moléculaire, Université de Liège, Belgique
During brain ontogenesis, the temporal and spatial generation of the different types of
neuronal and glial cells from precursors occurs as a sequence of successive progenitor stages
whose proliferation, survival and cell-fate choice are controlled by environmental and cellular
regulatory molecules. Neurotransmitters belong to the chemical microenvironnement of neural
cells, even at the earliest stages of brain development. It is now established that specific neurotransmitter
receptors are present on progenitor cells of the developing central nervous system
(CNS) and could play, during neural development, a role that has remained unsuspected until
recently (for a review, see publication of Nguyen et al., 2000).
In a recent study using immunocytochemistry and RT-PCR, which will be presented for publication
in NeuroReport, we show that glycine ionotropic receptors (GlyRs) are expressed by postnatal
rat striatum-derived nestin positive cells within neurospheres. By means of whole-cell patchclamp
technique, we have moreover recorded strychnine-sensitive reversible inward currents
triggered by glycine in these cells. Our results support therefore the functional expression of
GlyRs in neurospheres by nestin positive neural progenitors likely including neural stem cells
(NSCs). Furthermore, we have observed that NSCs also show modifications of their membrane
conductance in response to the application of other transmitters (GABA, glutamate, acetylcholine
and serotonin).
In parallel, we have developed a new culture assay allowing both fast isolation and expansion
of rat striatal multipotent progenitors that express PSA-NCAM, a marker which is a hallmark
of cells close to NSCs but likely committed to the glial lineage. This defined model of an
almost pure cell population will help us to better address the effects of neurotransmitters on neural
progenitors proliferation, differentiation and migration capacities.
Astroglial control of neuronal excitability and survival
Rigo, J.M. 1 , Belachew, S. 1 , Hans, G., Malgrange, B. 1 , Rocher, V. 1 , Leprince, P. 1 , Kirchoff, F. 2 ,
Rogister, B. 1 and Moonen, G. 1
1 Centre de Neurobiologie Cellulaire et Moléculaire, Université de Liège, Belgique
2 Max Planck Institute for Experimental Medicine, Göttingen, Allemagne
As a reminder, the INItoxins are inhibitors of inhibitory neurotransmission (such as NAF or
β-carbolines) that are also neurotoxic (NAF is a neurotoxic astroglia-derived factor that also
behaves as a negative allosteric modulator of ligand-gated chloride channels).
Interactions of the INItoxins with ligand-gated chloride channels (the GABAAR
and the GlyR)
In a previous report, we showed that ∃β-carbolines (βCs), besides their well established
negative allosteric modulation of GABA AR-mediated responses, also act on strychnine-sensitive
135