Regulation of striatal preproenkephalin tnRNA levels in MPTP-lesioned mice treated with estradiol

We reported previously the protective effect of 17 beta-estradiol (17 beta-E-2) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine (DA) depletion. This protection was stereospecific, because 17 beta-E-2 showed activity but 17 alpha-estradiol (17 alpha-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 17 beta-E-2. Protection against MPTP-induced DA depletion was obtained with 17 beta-E-2 but not 17 alpha-E-2. MPTP lesion increased striatal preproenkephalin (PPE) mRNA levels and they remained elevated in 17 alpha-E-2-treated MPTP mice whereas 17 beta-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 17 beta-E-2: on PPE mRNA after a lesion could be one of many mechanisms by which this steroid exerts its neuroprotective activity. (c) 2005 Wiley-Liss, Inc.