Estrogen provides neuroprotection against activated microglia-induced dopaminergic neuronal injury through both estrogen receptor-alpha and estrogen receptor-beta in microglia

Autor: Yan Zhao, Weidong Le, Xuping Li, Xuan Liu, Xiao Lan Fan, Rui Li, Guang Rui Luo
Rok vydání: 2005
Předmět:
Zdroj: Journal of neuroscience research. 81(5)
ISSN: 0360-4012
Popis: Estrogen provides neuroprotection against neurodegenerative diseases, including Parkinson’s disease. Its effects may stem from interactions with neurons, astrocytes, and microglia. We demonstrate here in primary cultures of rat mesencephalic neurons that estrogen protects them from injury induced by conditioned medium obtained from lipopolysaccharide (LPS)-activated microglia. LPS-induced nitrite production and tumor necrosis factor-a up-regulation in microglia were blocked by estrogen pretreatment. Estrogen neuroprotection was related to microglial activation of estrogen receptors (ERs), insofar as the protective effect of the microglia-conditioned medium was overridden by pretreatment of microglia with the ER antagonist ICI 182,780. On the other hand, the specific ERa antagonist, MPP dihydrochloride, only partially blocked the effects of estrogen, suggesting that estrogen protection was mediated via both ERa and ERb. LPS treatment did not change ERa mRNA levels in microglia, astrocytes, and neurons, but it up-regulated ERb mRNA levels in microglia and astrocytes. Similarly, increased ERb protein levels were detected in LPS-activated microglia. More interesting was that immunocytochemical analysis revealed that ERb was localized in the cytoplasm of microglia and in the cell nucleus of astrocytes and neurons. In summary, our results support the notion that estrogen inhibits microglial activation and thus exhibits neuroprotective effects through both ERa and ERb activation. The cytoplasm location of microglial ERb suggests the possible involvement of nonclassical effects of estrogen on microglia. Changes in microglial ERb expression levels may modulate such effects of estrogen. V C 2005 Wiley-Liss, Inc. Parkinson’s disease (PD) has been accepted for a long time to be more prevalent in males than in females, with a relative male to female ratio of 1.4 to 3.7. This sexual difference has recently been confirmed again by using metaanalysis to analyze the results from seven studies (Wooten et al., 2004). The reason for this gender difference is not fully understood. There is some indication that levels of estrogens or progesterones or differences in their cognate receptor levels could account for this disparity. For example, estrogen deficiency following menopause might partially explain age and gender differences in late-onset dopaminergic (DA)-related disorders (Craig
Databáze: OpenAIRE
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