Regulation of striatal preproenkephalin mRNA levels in MPTP-lesioned mice treated with estradiol.
We reported previously the protective effect of 17beta-estradiol (17beta-E(2)) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine (DA) depletion. This protection was stereospecific, because 17beta-E(2) showed activity but 17alpha-estradiol (17alpha-E(2)) did not. The mechanisms by which estradiol exerts its beneficial effects, however, remain unknown. We investigated a possible implication of enkephalins (ENK) in neuroprotective activity of 17beta-E(2). Protection against MPTP-induced DA depletion was obtained with 17beta-E(2) but not 17alpha-E(2). MPTP lesion increased striatal preproenkephalin (PPE) mRNA levels and they remained elevated in 17alpha-E(2)-treated MPTP mice whereas 17beta-E(2) treatment decreased these levels to control values. This is the first report of estradiol modulation of striatal PPE mRNA in mice. Negative and significant correlations between DA levels, vesicular monoamine transporter (VMAT(2)) density, and PPE mRNA were observed in the striatum of lesioned animals. This effect of 17beta-E(2) on PPE mRNA after a lesion could be one of many mechanisms by which this steroid exerts its neuroprotective activity.
D'Astous
Myreille
M
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, Quebec City, Quebec, Canada.
Morissette
Marc
M
Callier
Sophie
S
Di Paolo
Thérèse
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004745:Enkephalins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D017403:In Situ Hybridization; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011498:Protein Precursors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects*; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D004745:Enkephalins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D018696:Neuroprotective Agents; D011498:Protein Precursors; D012333:RNA, Messenger; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; D015102:3,4-Dihydroxyphenylacetic Acid; D004958:Estradiol; C033660:preproenkephalin; D004298:Dopamine; D006719:Homovanillic Acid