Role of laminin bioavailability in the astroglial permissivity for neuritic outgrowth.
The mechanisms involved in the failure of an adult brain to regenerate post-lesion remain poorly understood. The reactive gliosis which occurs after an injury to the CNS and leads to the glial scar has been considered as one of the major impediments to neurite outgrowth and axonal regeneration. A glial scar consists mainly of reactive, hypertrophic astrocytes. These reactive cells acquire new properties, leading to A non-permissive support for neurons. Astrogial reactivity is mainly characteriized by a high overexpression of the major component of the gliofilaments, the glial fibrillary acidic protein (GFAP). This GFAP overexpression is related to the astroglial morphological response to injury. We hypothesized that modulation of GFAP synthesis, reversing the hypertrophic phenotype, might also reverse the blockage of neuritic outgrowth observed after a lesion. In this article, we review findings of our group, confirming our hypothesis in a model of lesioned neuron-astrocyte cocultures. We demonstrate that permissivity for neuritic outgrowth is related to phenotypic changes induced in reactive astrocytes transfected by antisense GFAP-mRNA. We also found that this permissivity was related to a neuron-regulated extracellular laminin bioavailability.
Tardy
Marcienne
M
INSERM U-421, IM3, Medical Faculty and Biocheemistry Department CHU Henri Mondor, 94010 Creteil, France. tardy@im3.inserm.fr
D000328:Adult; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D018920:Coculture Techniques; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006801:Humans; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000502:physiology*; D009414:Nerve Growth Factors; D009416:Nerve Regeneration / Q000502:physiology; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D012377:Rodentia
D005904:Glial Fibrillary Acidic Protein; D007797:Laminin; D009414:Nerve Growth Factors