Critical period for dopaminergic neuroprotection by hormonal replacement in menopausal rats.

Abstract:

: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-α 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 α agonists. In microglial cells, estrogen receptor β 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 α and renin-angiotensin system play a major role.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Rodriguez-Perez AI,Borrajo A,Valenzuela R,Lanciego JL,Labandeira-Garcia JL

doi

10.1016/j.neurobiolaging.2014.10.028

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

1194-208

issue

2

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(14)00688-5

journal_volume

36

pub_type

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