The expression of proenkephalin and prodynorphin genes and the induction of c-fos gene by dopaminergic drugs are not altered in the straitum of MPTP-treated mice.
The expression of proenkephalin (PENK), prodynorphin (PDYN) and c-fos genes was studied in the striatum of C57B1/6 mice treated with 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP), which are used as a rodent model of Parkinson's disease (PD). Two weeks after systemic administration of MPTP (2 x 40 mg/kg, s.c. 18h apart), the lesion of the substantia nigra (SN) could be visualised by loss of the nigral tyrosine hydroxylase (TH) mRNA hybridization signal and by a 91% decrease in striatal dopamine levels. The levels of PENK and PDYN mRNAs were not significantly changed in the striatum of the lesioned mice, as compared to non-treated controls. The induction of the immediate early gene c-fos by the dopamine D2 receptor antagonist haloperidol was not altered, while the selective D1 receptor agonist SKF 38393 failed to induce c-fos in the striatum of MPTP-treated mice. These results are in contrast to the data concerning rats with the 6-hydroxydopamine (6-OHDA) lesion of the SN, which serve as another rodent model of PD. In the striata of 6-OHDA-lesioned rats, PENK gene is upregulated, PDYN gene is down-regulated and the induction of c-fos gene by D2 receptor antagonists is abolished, whereas selective D1 receptor agonists induce c-fos gene, which does not occur in non-lesioned rats. We presume that the lack of influence of the MPTP lesion in mice on the striatal gene expression was mainly caused by insufficient dopamine depletion in the striatum, which could not be increased in this model. The importance of the changes observed in 6-OHDA-lesioned rats has been discussed in the context of the mouse and primate MPTP models of PD.
Ziolkowska
B
B
Neuropeptide Research Department, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Horn
G
G
Kupsch
A
A
Höllt
V
V
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D018491:Dopamine Agonists; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine