ENHANCED RECOVERY OF THE NIGROSTRIATAL DOPAMINERGIC SYSTEM IN MPTP-TREATED MICE FOLLOWING INTRASTRIATAL INJECTION OF BASIC FIBROBLAST GROWTH-FACTOR IN RELATION TO AGING

Studies have suggested that the restorative effects of adrenal medulla ry chromaffin cell grafts in animal models of Parkinson's disease may be related to trophic factors contained within the chromaffin cells. B asic fibroblast growth factor (bFGF) is present in chromaffin cells an d has been shown to exert trophic effects on dopaminergic neurons in v itro. Basic FGF was stereotaxically injected into the striatum of youn g (2-month-old) and aging (12-month-old) C57BL/6 mice which had been t reated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1 week earlier. MPTP treatment reduced tyrosine hydroxylase (TH)-immunoreact ive (IR) fibers in the striatum and striatal dopamine (DA) concentrati on in both the young and older mice 5 weeks later. Computerized image analysis of striatal DA fibers in young mice treated with bFGF showed significant recovery of DA fibers up to 600 mum from the injection sit e 5 weeks after MPTP administration. Striatal DA fibers in older mice treated with bFGF showed significant recovery only up to 300 mum from the injection site, and the degree of recovery was very limited compar ed with young mice. HPLC analysis of DA concentration revealed that st riatal DA in young mice recovered significantly when treated with bFGF , but no significant recovery was observed in older mice. It is conclu ded that bFGF enhances the recovery of striatal DA systems from MPTP t oxicity both in young and in older mice, but that such benefits are ve ry limited in older mice.