Epidermal growth factor enhances striatal dopaminergic parameters in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse.
Intracerebroventricular infusion of epidermal growth factor (EGF) into mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced degeneration of dopaminergic nigrostriatal neurons partially enhanced the content of dopamine (DA) and 3,4-dihydroxyphenylacetic acid as well as the activity of tyrosine hydroxylase in the striatum. EGF also enhanced these parameters in control, unlesioned animals. Neurotrophic activity also was observed in embryonic mesencephalic cultures, where EGF enhanced DA uptake after a lesion with the neurotoxic metabolite of MPTP, 1-methyl-4-phenylpyridinium ion. Our in vivo and in vitro studies suggest that EGF may be a neurotrophic factor for dopaminergic neurons, or may act indirectly by inducing the release of a dopaminergic trophic factor from other cells.
Department of Psychiatry, Ohio State University College of Medicine, Columbus 43210-1239.
M
M
Hadjiconstantinou
J G
JG
Fitkin
A
A
Dalia
N H
NH
Neff
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D012016:Reference Values; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D015102:3,4-Dihydroxyphenylacetic Acid; D004815:Epidermal Growth Factor; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine