MPTP-induced increase in c-Fos- and c-Jun-like immunoreactivity in the monkey cerebellum.
The transcription factors c-Fos and c-Jun have been described to be overexpressed following many pathological stimuli, but whether they are required for neurodegeneration or neuroprotection is still open. In the present report, we analyzed the role of c-Fos and c-Jun proteins in Purkinje cell degeneration caused by the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the monkey cerebellum, and determined the neuroprotective effect of the antioxidant drug a-dihydroergocryptine (DHEC), whose prior and simultaneous administration reduced the MPTP-induced neuronal loss in the substantia nigra. Immunocytochemistry for c-Fos- and c-Jun-like proteins showed persistent increased staining in Purkinje cells of MPTP-treated monkeys. The staining was greatly reduced in animals receiving DHEC. Similar results were observed in white matter glial cells after immunoreaction for c-Fos. The results suggest that, at least as far as the cerebellum is concerned, the increase in c-Fos and c-Jun expression correlate with cell damage, rather than with preservation.
Necchi
Daniela
D
Dipartimento di Biologia Animale, Laboratorio di Biologia Cellulare e Neurobiologia, Università di Pavia, Piazza Botta 10, 27100 Pavia, Italy. necchi.d@unipv.it
Soldani
C
C
Ronchetti
F
F
Bernocchi
G
G
Scherini
E
E
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D011689:Purkinje Cells / Q000187:drug effects; D015854:Up-Regulation
D015259:Dopamine Agents; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine