期刊
NEUROBIOLOGY OF AGING
卷 36, 期 2, 页码 1194-1208出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.10.028
关键词
Critical period; Estrogen; Menopause; Ovariectomy; Parkinson
资金
- Spanish Ministry of Science and Innovation
- Spanish Ministry of Health [RD12/0019/0020, BFU2012-37087]
- Spanish Ministry of Health (CIBERNED)
- Galician Government (XUGA)
- Galician Government [GRC2014/002]
- European Regional Development Fund (FEDER)
The neuroprotective effects of menopausal hormonal therapy in Parkinson's disease have not yet been clarified, and it is not known whether there is a critical period. Estrogen induced significant protection against 6-hydroxydopamine-induced dopaminergic degeneration when administered immediately or 6 weeks, but not 20 weeks after ovariectomy. In the substantia nigra, ovariectomy induced a decrease in levels of estrogen receptor-alpha and increased angiotensin activity, NADPH-oxidase activity, and expression of neuroinflammatory markers, which were regulated by estrogen administered immediately or 6 weeks but not 20 weeks after ovariectomy. Interestingly, treatment with angiotensin receptor antagonists after the critical period induced a significant level of neuroprotection. In cultures, treatment with 1-methyl-4-phenylpyridinium induced an increase in astrocyte-derived angiotensinogen and dopaminergic neuron death, which were inhibited by estrogen receptor alpha agonists. In microglial cells, estrogen receptor beta agonists inhibited the angiotensin-induced increase in inflammatory markers. The results suggest that there is a critical period for the neuroprotective effect of estrogen against dopaminergic cell death, and local estrogen receptor alpha and renin-angiotensin system play a major role. (C) 2015 Elsevier Inc. All rights reserved.
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