Basic fibroblast growth factor enhances the growth of postnatal neostriatal GABAergic neurons in vitro.
Basic fibroblast growth factor (bFGF) significantly enhances the short-term survival of embryonic striatal neurons in vitro but has little effect on the outgrowth of striatal cells compared to neurons from other brain regions. Studies in our laboratory have shown that bFGF protects postnatal striatal cells in vitro from NMDA receptor-induced neurotoxicity. We therefore examined the effects of bFGF on the outgrowth of GABA-containing cells taken from the postnatal (Day 1) caudate-putamen and cultured for up to 3 weeks. In control cultures GABAergic neurons formed three populations based on somatic size and developed the cytoarchitectural features characteristic of dendrites, spines, and axons. In the presence of bFGF (6 pM continuously from the day of plating), small- and medium-sized GABAergic neurons showed significant increases compared to untreated controls in axon-like growth (axon length) at 6 days in culture and in both axon- and dendrite-like neurite growth (axon length and branch order, number of primary dendrites, dendrite length, and dendritic branch order) at 13 and 17 days in culture. Large GABAergic neurons were unaffected by treatment with bFGF. Striatal GABAergic neurons exposed to nerve growth factor (10 ng/ml) were not different from untreated controls. Neuron survival was also unaffected by bFGF treatment at all days in culture examined. Other observations suggested that the neurotrophic effects of bFGF were mediated by a direct action of the growth factor on striatal neurons and not glial cells. First, glial cells (identified by the immunohistochemical localization of glial fibrillary acidic protein) were unaffected by bFGF treatment at the low concentration (6 pM) used to enhance neurite growth, but did significantly proliferate at higher concentrations of bFGF (6 nM). Second, immunoreactive bFGF receptor protein was localized predominantly to the somata and processes of striatal neurons and not to glial cells in the cultures. Finally, when neurons from control cultures were briefly exposed (1 to 4 h) to bFGF at concentrations which were neurotrophic, a marked elevation in the immediate early gene protein c-fos was observed by immunohistochemistry in the nuclei of neurons, including GABAergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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Department of Neurology, Massachusetts General Hospital, Boston 02114.
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D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D007150:Immunohistochemistry; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D005680:gamma-Aminobutyric Acid