Julien Gras

Publications (2)16.57 Total impact

• Article: Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system.

  Gabrièle Piaton, Marie-Stéphane Aigrot, Anna Williams, Sarah Moyon, Vanja Tepavcevic, Imane Moutkine, Julien Gras, Katherine S Matho, Alain Schmitt, Heidi Soellner, Andrea B Huber, Philippe Ravassard, Catherine Lubetzki
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  ABSTRACT: Oligodendrocyte precursor cells, which persist in the adult central nervous system, are the main source of central nervous system remyelinating cells. In multiple sclerosis, some demyelinated plaques exhibit an oligodendroglial depopulation, raising the hypothesis of impaired oligodendrocyte precursor cell recruitment. Developmental studies identified semaphorins 3A and 3F as repulsive and attractive guidance cues for oligodendrocyte precursor cells, respectively. We previously reported their increased expression in experimental demyelination and in multiple sclerosis. Here, we show that adult oligodendrocyte precursor cells, like their embryonic counterparts, express class 3 semaphorin receptors, neuropilins and plexins and that neuropilin expression increases after demyelination. Using gain and loss of function experiments in an adult murine demyelination model, we demonstrate that semaphorin 3A impairs oligodendrocyte precursor cell recruitment to the demyelinated area. In contrast, semaphorin 3F overexpression accelerates not only oligodendrocyte precursor cell recruitment, but also remyelination rate. These data open new avenues to understand remyelination failure and promote repair in multiple sclerosis.
  Brain 03/2011; 134(Pt 4):1156-67. · 9.46 Impact Factor
• Article: Turnover of newborn olfactory bulb neurons optimizes olfaction.

  Aurélie Mouret, Gabriel Lepousez, Julien Gras, Marie-Madeleine Gabellec, Pierre-Marie Lledo
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  ABSTRACT: Postdevelopmental neurogenesis occurs in the olfactory bulb (OB), to which new interneurons are continuously recruited. However, only a subset of the adult-generated interneurons survives, as many undergo programmed cell death. As part of homeostatic processes, the removal of new neurons is required alongside the addition of new ones, to ensure a stable neuron number. In addition to a critical role in tissue maintenance, it is still unclear whether this neuronal elimination affects the functioning of adult circuits. Using focal drug delivery restricted to the OB, we investigated the significance of programmed cell death in the adult OB circuits. Cell death was effectively blocked by the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD). The zVAD effect differed with newborn interneuron location, either in the superficial (periglomerular cells) or in the deep (granule cells) OB layers. Furthermore, whereas sensory experience potentiated the effect of zVAD on the survival of new granule cells, it had no additional effect on the survival of new periglomerular cells. Thus, distinct mechanisms control the survival/elimination decision of newborn interneuron subtypes. However, zVAD had no effect on the olfactory sensory neurons projecting to the bulb. Remarkably, psychophysical analyzes revealed that a normal rate of new neuron elimination was essential for optimal odorant exploration and discrimination. This study highlights the importance of cell elimination for adjusting olfactory performance. We conclude that adult-generated OB interneurons are continually turned over, rather than simply added, and the precise balance between new and mature interneurons, set through active selection/elimination processes, is essential for optimizing olfaction.
  Journal of Neuroscience 09/2009; 29(39):12302-14. · 7.11 Impact Factor