Effects of fibroblast growth factors on MPTP-induced parkinsonian syndrome in mice

Abstract

Acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) have been shown to possess neuroprotective action on dopaminergic neurons of substantia nigra (SN) in vitro and in vivo. In order to assess the role of aFGF and bFGF in the development of parkinsonian syndrome (PS) we examined changes in animal motor activity and expression of parkinsonian symptoms—oligokinesia, rigidity and tremor in C57BL/6 mice with PS induced by nigrostriatal dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, intraperitoneally, 20 mg/kg, twice a day, every 12 h for 10 days). MPTP administration caused oligokinesia, rigidity, weight loss and reduced survival in mice on day 5 after the beginning of treatment. Bilateral intranasal infusion of both aFGF and bFGF (3.0 μg per mouse 30 min before, 3 and 5 days after the beginning of MPTP administration) increased animal motor activity and reduced rigidity, as well aFGF suppressed tremor. bFGF, but not aFGF, prevented animal weight loss and lowering of survival. Morphological studies revealed the decrease of damaged nigral neurons number in mice with PS subjected to intranasal aFGF or bFGF infusion (at 63 and 72%, correspondingly). It is thus suggested that the observed antiparkinsonian protective effects of aFGF and bFGF in mice with experimental PS may be due to the trophic influence of FGFs which weakens and retards degeneration and prevents death of nigrostriatal dopaminergic neurons.