Dopamine differentiation factors increase striatal dopaminergic function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice.
We have previously shown that muscle-derived differentiation factors (MDF) and human recombinant acidic fibroblast growth factor (aFGF) have beneficial behavioral and neurochemical effects on the nigrostriatal dopaminergic neurons of 6-hydroxy-dopamine (6-OHDA)-lesioned rats (Jin and Iacovitti: Neurobiol Dis 2:1-12, 1995). In the present study, we determined the effects of similar treatments on mice treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Five days after unilateral striatal infusion of MDF or aFGF into MPTP-lesioned mice, striatal tyrosine hydroxylase (TH) activity and dihydroxyphenylacetic acid (DOPAC) levels were bilaterally increased (20-35%) compared to untreated (lesion only) or control (phosphate buffered saline + bovine serum albumin) mice. These increases, however, were not accompanied by change in dopamine (DA) levels, indicating an elevation of DA synthesis (TH/DA) and turnover (DOPAC/DA). The present findings that MDF and aFGF may have neurochemical effects in vivo on the lesioned nigrostriatal dopaminergic system suggest their potential pharmacological role in the treatment of Parkinson's disease.
Jin
B K
BK
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, Pennsylvania, USA.
Iacovitti
L
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D007839:Functional Laterality; D007700:Kinetics; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000633:toxicity; D012016:Reference Values; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D016220:Fibroblast Growth Factor 1; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine