Effects of estrogens on striatal damage after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in male and female mice

• Published in: Molecular and cellular endocrinology Vol. 296; no. 1; pp. 87 - 93
• Main Authors: Ookubo, Masanori, Yokoyama, Hironori, Takagi, Sho, Kato, Hiroyuki, Araki, Tsutomu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 16.12.2008
• Subjects: 3,4-Dihydroxyphenylacetic Acid - metabolism; Animals; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Cytoprotection - drug effects; Dopamine - metabolism; Dopamine system; Drug Evaluation, Preclinical; Estrogen; Estrogens - pharmacology; Estrogens - therapeutic use; Estrone - pharmacology; Female; Homovanillic Acid - metabolism; Male; Mice; Mice, Inbred C57BL; MPTP Poisoning - pathology; MPTP Poisoning - prevention & control; Parkinson's disease; Time Factors; Western blot analysis; Mice; Parkinson's disease; Western blot analysis; Dopamine system; Estrogen
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2008.07.019

Emerging evidence shows a beneficial effect of estrogens for Parkinson's disease, yet the exact potency of these compounds implicated remain obscured. In this study, we investigated the neuroprotective effect of 17β-estradiol and estrone against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal toxicity in mice. The neuroprotective effects of both compounds were evaluated by HPLC and Western blot analyses 5 days after the last of 4 consecutive injections of MPTP at 1-h intervals to mice. Subacute treatment (10 days) with estrone or 17β-estradiol at low doses (0.05 and 0.2 mg/kg) showed no significant changes against MPTP-induced damage of striatal dopamine terminals in mice. Furthermore, acute treatment with estrone at high doses (0.5 and 2.0 mg/kg) showed no significant alterations against MPTP-induced damage of striatal dopamine terminals in mice. In contrast, acute treatment with 17β-estradiol at high doses exhibited a neuroprotective effect against the damage of striatal dopamine terminals in both male and female mice after MPTP treatments. The results demonstrate that estrogen therapy with high doses may have a neuroprotective effect on the damage of striatal dopamine terminals in the MPTP-induced mice. These findings may lead to be development of estrogen therapy for the prevention and treatment of Parkinson's disease.