Sequential up-regulation of the c-fos, c-jun and bax genes in the cortex, striatum and cerebellum induced by a single injection of a low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in C57BL/6 mice.
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.
Chen
J Y
JY
Department of Pediatrics, Taipei Medical University, Taipei 110, Taiwan.
Hsu
P C
PC
Hsu
I L
IL
Yeh
G C
GC
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects* / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine