MPTP-treated young mice but not aging mice show partial recovery of the nigrostriatal dopaminergic system by stereotaxic injection of acidic fibroblast growth factor (aFGF).
Acidic fibroblast growth factor (aFGF) is a heparin-binding polypeptide that acts as a neurotrophic factor for certain central and peripheral neurons. Acidic FGF was injected stereotaxically into the striatum of young (2-month-old) and aging (12-month-old) C57BL/6 mice that were treated 1 week before with systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP treatment (4 x 20 mg/kg, i.p. given 12 h apart) reduced tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in the striatum and reduced dopamine (DA) concentration to 32% of the controls in young and 20% of the controls in aging mouse brain 5 weeks after administration. Although the DA concentration recovered to 43% of the controls in young mice following stereotaxic injection of aFGF 5 weeks after MPTP treatment, aging mice with such treatment did not show a significant recovery of DA concentration. Computerized image analysis of TH-IR fibers in the striatum also showed significant recovery in young mice treated with aFGF, while aging mice did not show a significant recovery. We conclude that treatment of MPTP-depleted young mice with aFGF results in partial recovery in the nigrostriatal DA system but such benefits decline with age.
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Department of Neurobiology and Anatomy, University of Rochester School of Medicine, NY 14642.
Notter
M F
MF
Felten
S Y
SY
Felten
D L
DL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D007267:Injections; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010300:Parkinson Disease / Q000188:drug therapy; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D016220:Fibroblast Growth Factor 1; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine