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Critical period for dopaminergic neuroprotection by hormonal replacement in menopausal rats

Autores: Rodríguez-Pérez, A. I.; Borrajo, A.; Valenzuela, R.; Lanciego Pérez, José Luis; Labandeira-García, J. L.
Título de la revista: NEUROBIOLOGY OF AGING
ISSN: 0197-4580
Volumen: 36
Número: 2
Páginas: 1194 - 1208
Fecha de publicación: 2015
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-¿ 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 ¿ agonists. In microglial cells, estrogen receptor ß 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 ¿ and renin-angiotensin system play a major role.