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.