Regulation of astroglial-derived dopaminergic neurotrophic factors by interleukin-1 beta in the striatum of young and middle-aged mice.
Interleukin-1 beta (IL-1 beta) can induce dopaminergic axonal sprouting in the denervated striatum of parkinsonian animals. In order to determine whether IL-1 beta effects on dopaminergic axonal sprouting are mediated by the induction of astroglial-derived dopaminergic neurotrophic factors, effects of IL-1 beta treatment on acidic and basic fibroblast growth factor (aFGF and bFGF) and glial cell line-derived growth factor (GDNF) gene expression were examined in primary striatal astrocyte cultures and after in vivo administration. We found a selective induction of bFGF mRNA synthesis but not aFGF or GDNF mRNA after IL-1 beta treatment both in vitro and in vivo. This suggests that bFGF may be the putative endogenous dopaminergic neurotrophic factor mediating lesion-induced plasticity of dopamine neurons. In addition, to determine why recovery from injury becomes reduced with age, we examined whether there was an aging-associated decline in the ability of IL-1 beta to induce the synthesis of neurotrophic factors in middle-aged animals compared to young mice. Interestingly, IL-1 beta stimulated a greater induction in bFGF mRNA levels in the middle-aged mice compared to young mice. These results suggest that the regulation of bFGF and possibly its receptor signaling efficacy may vary as the brain ages.
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Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Blum
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D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004298:Dopamine / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics; D010300:Parkinson Disease / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
D018076:DNA, Complementary; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007375:Interleukin-1; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004298:Dopamine