FGF-2 modulates dopamine and dopamine-related striatal transmitter systems in the intact and MPTP-lesioned mouse.
Following a previous study in which we showed ameliorative effects of basic fibroblast growth factor (FGF-2) locally applied to the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice, we investigated FGF-2 actions at different time intervals after the lesion and effects on non-dopaminergic striatal transmitter systems. A triple intraperitoneal injection of 30 mg/kg MPTP at 24 h intervals caused a reduction of striatal dopamine to 23% of control levels that lasted for at least 4 weeks. Four micrograms FGF-2 soaked into gel foam and placed onto the right striatum partially and bilaterally restored dopamine levels and tyrosine hydroxylase activity after 2 weeks, when the treatment started simultaneously or 1 day after the toxin lesion. FGF-2 was ineffective, if administration commenced with a delay of 7 days. Striatal neurotransmitters that are known to be linked to the dopaminergic system were also altered by the MPTP treatment. GABA was significantly increased, while somatostatin levels were reduced. Upon FGF-2 administration both GABA and somatostatin levels were partially normalized. Our data are consistent with the notion that FGF-2 protects and rescues acutely and subacutely MPTP-lesioned nigrostriatal neurons and that its effects must be mainly indirect. Likewise, positive effects of FGF-2 on non-dopaminergic neurons may be due to the partial restoration of striatal dopamine.
Otto
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University of Heidelberg, Department of Anatomy and Cell Biology, Germany.
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D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018377:Neurotransmitter Agents; D016222:Fibroblast Growth Factor 2; D013373:Substance P; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine