Tyrosine hydroxylase and aromatic L-amino acid decarboxylase in mesencephalic cultures after MPP+: the consequences of treatment with GM1 ganglioside.
Rat embryonic mesencephalic cultures were treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+), and GM1 ganglioside added after the toxin. Twelve days after a 24-h exposure to MPP+, there was a significant decrement in tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AAAD) activities. In addition, TH mRNA was decreased, whereas AAAD mRNA was no different from control cultures. Adding GM1 to control unlesioned cultures had no effect on TH activity or mRNA. In contrast, GM1 modestly increased both the activity and mRNA for AAAD. In the MPP+-treated cultures, GM1 induced a partial recovery of TH and AAAD activity and increased mRNA for both above unlesioned control levels. Our studies demonstrate that GM1 upregulates the synthetic enzymes for dopamine in MPP+-lesioned embryonic mesencephalic cultures, and suggest that TH and AAAD respond differentially to the neurotoxin insult.
Dalia
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A
Department of Pharmacology, The Ohio State University College of Medicine, Columbus 43210, USA.
Neff
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NH
Hadjiconstantinou
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M
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D005260:Female; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D008636:Mesencephalon / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects*
D005677:G(M1) Ganglioside; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D015655:1-Methyl-4-phenylpyridinium