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Mohamed Jaber, séminaire BN dans le cadre du DU , maladies neurodégénératives "Neurodegenerative disorders and cell therapies"

Abstract :


Cell replacement therapy has been proposed as a possible mean to replace lost dopamine neurons in Parkinson’s disease (PD).
In most studies, the transplanted cells have been placed within the target sites, the striatum, and not within the lesioned site, the substantia nigra (SN), as the adult nigro-striatal pathway was thought to constitute a non-permissive environment for long distance axonal outgrowth of transplanted embryonic neurons. A growing body of evidence has recently challenged this concept and proposed instead to place the graft within its ontogenic site. For instance, we have shown that transplanted neurons within the lesioned motor cortex can send distant and appropriate projections to target areas including the spinal cord (Nature Neurosciences, 2007). More recently, we have extended these findings to a PD animal model where we have shown that embryonic cells transplanted within the pre-lesioned SN can send projections to the striatum and, to a lesser extent, the frontal cortex and the nucleus accumbens (Neurobiology of Disease, 2009). This have lead us to propose that homotopic transplantation can be an alternative in cell based therapies as transplanted neurons can integrate within the host brain, send massive projections to target areas, restore the damaged circuitry, increase neurotransmitter levels and ameliorate behavior (Trends in Neurosci., 2011). As the use of embryonic cells is not without ethical and logistical burden, we have also transplanted stem-cells derived neurons within the new born brain and again showed that these cells can extend axons to target areas (Nature, 2008).While the field of cell replacement therapies has been recently called into question with contrasting results in transplanted Parkinson’s disease patients, we believe that our current work and projects may raise reasonable hopes and open new avenues in this field.

 

L'équipe de Mohamed Jaber a réalisé un exploit en septembre 2007 en transplantant avec succès des neurones embryonnaires dans le cortex moteur lésé de souris adultes. En effet, ces neurones ont établi les contacts adéquats avec les neurones des souris receveuses et ont même développé des fibres nerveuses jusqu'à la moelle épinière. Des travaux qui font tomber le dogme en vigueur depuis les premières tentatives de greffes – il y a une trentaine d'années –, selon lequel le cerveau adulte ne permet pas le développement des neurones transplantés. Plus important, ils ouvrent de nouvelles stratégies pour reconstruire des voies nerveuses centrales endommagées et traiter certaines maladies neurodégénératives telles celles d'Huntington et de Parkinson, dans lesquelles les zones en souffrance sont assez restreintes (CNRS)

Selected publications

B. Giros, M. Jaber, S. R. Jones, R. M. Wightman and M. G. Caron. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature, 379 (1996) 606-612.
M. Jaber, W. J. Koch, H. A. Rockman, B. Smith, R. A. Bond, K. Sulik, J. Ross Jr., R. J. Lefkowitz, M. G. Caron and B. Giros. Essential role of b adrenergic receptor kinase 1 in cardiac development and function. Proc. Natl. Acad. Sci. USA 93 (1996) 12974-12979.

R. Gainetdinov, W. C. Wesel, S. R. Jones, E. Levin, M. Jaber and M. G. Caron. Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283 (1999) 397-401.

A. Gaillard, B. Dumartin, L. Prestoz, A. Cantereau, F. Morel, M. Roger and M. Jaber. Reestablishment of damaged adult motor pathways by grafted embryonic cortical neurons. Nature Neurosci. (2007) 10(10) : 1294 – 1299.

Solinas M, Chauvet C, Thiriet N, El Rawas R, Jaber M. Reversal of cocaine addiction by environmental enrichment. Proc. Natl. Acad. Sci, USA (2008) 105(44):17145-50.

Bertrand Bloch et de François Tison de l'IMN