Abstract
We investigated whether single injection of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) (20 mg/kg) will alter the expression of pro-apoptotic genes, namely, the c-fos, c-jun, and bax, in the striatum, cortex, and cerebellum of adult male C57BL/6 mice using reverse transcription-polymerase chain reaction assay. Injection of MPTP induced a transient decrease in the content of tyrosine hydroxylase estimated by the immunoreactivity in the striatum, which completely recovered 14 day after injection. A rapid but transient up-regulation of c-fos and c-jun genes occurred an hour after MPTP-injection, and a delayed but persistent up-regulation of bax gene expression occurred 3 day after injection. The up-regulation of these genes was present in all the examined brain regions. This result suggests that MPTP, at a low dose causing transient degeneration in the striatum, is capable of triggering two genetic pathways related to the generation of apoptosis in both dopaminergic and non-dopaminergic systems in the mouse brain.
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
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Animals
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Apoptosis / drug effects*
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Apoptosis / physiology
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Brain / drug effects*
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Brain / metabolism
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Brain / physiopathology
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Cerebellum / drug effects
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Cerebellum / metabolism
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Cerebellum / physiopathology
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Cerebral Cortex / physiopathology
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Dopamine / metabolism
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Male
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Mice
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Mice, Inbred C57BL
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Neostriatum / drug effects
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Neostriatum / metabolism
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Neostriatum / physiopathology
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Parkinsonian Disorders / genetics*
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Parkinsonian Disorders / metabolism
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Parkinsonian Disorders / physiopathology
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Proto-Oncogene Proteins / drug effects*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-bcl-2*
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Proto-Oncogene Proteins c-fos / drug effects*
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-jun / drug effects*
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Proto-Oncogene Proteins c-jun / genetics
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Tyrosine 3-Monooxygenase / metabolism
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Up-Regulation / drug effects*
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Up-Regulation / genetics
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bcl-2-Associated X Protein
Substances
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Bax protein, mouse
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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bcl-2-Associated X Protein
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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Tyrosine 3-Monooxygenase
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Dopamine