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Estrogen provides neuroprotection against activated microglia-induced dopaminergic neuronal injury through both estrogen receptor-alpha and estrogen receptor-beta in microglia.
J Neurosci Res. 2005 Sep 01; 81(5):653-65.JN

Abstract

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-alpha 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 ERalpha antagonist, MPP dihydrochloride, only partially blocked the effects of estrogen, suggesting that estrogen protection was mediated via both ERalpha and ERbeta. LPS treatment did not change ERalpha mRNA levels in microglia, astrocytes, and neurons, but it up-regulated ERbeta mRNA levels in microglia and astrocytes. Similarly, increased ERbeta protein levels were detected in LPS-activated microglia. More interesting was that immunocytochemical analysis revealed that ERbeta 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 ERalpha and ERbeta activation. The cytoplasm location of microglial ERbeta suggests the possible involvement of nonclassical effects of estrogen on microglia. Changes in microglial ERbeta expression levels may modulate such effects of estrogen.

Authors+Show Affiliations

Joint Laboratory of Institute of Biomedical Sciences, RuiJin Hospital, Shanghai Second Medical University, Shanghai, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16013043

Citation

Liu, Xuan, et al. "Estrogen Provides Neuroprotection Against Activated Microglia-induced Dopaminergic Neuronal Injury Through Both Estrogen Receptor-alpha and Estrogen Receptor-beta in Microglia." Journal of Neuroscience Research, vol. 81, no. 5, 2005, pp. 653-65.
Liu X, Fan XL, Zhao Y, et al. Estrogen provides neuroprotection against activated microglia-induced dopaminergic neuronal injury through both estrogen receptor-alpha and estrogen receptor-beta in microglia. J Neurosci Res. 2005;81(5):653-65.
Liu, X., Fan, X. L., Zhao, Y., Luo, G. R., Li, X. P., Li, R., & Le, W. D. (2005). Estrogen provides neuroprotection against activated microglia-induced dopaminergic neuronal injury through both estrogen receptor-alpha and estrogen receptor-beta in microglia. Journal of Neuroscience Research, 81(5), 653-65.
Liu X, et al. Estrogen Provides Neuroprotection Against Activated Microglia-induced Dopaminergic Neuronal Injury Through Both Estrogen Receptor-alpha and Estrogen Receptor-beta in Microglia. J Neurosci Res. 2005 Sep 1;81(5):653-65. PubMed PMID: 16013043.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Estrogen provides neuroprotection against activated microglia-induced dopaminergic neuronal injury through both estrogen receptor-alpha and estrogen receptor-beta in microglia. AU - Liu,Xuan, AU - Fan,Xiao-Lan, AU - Zhao,Yan, AU - Luo,Guang-Rui, AU - Li,Xu-Ping, AU - Li,Rui, AU - Le,Wei-Dong, PY - 2005/7/14/pubmed PY - 2005/11/3/medline PY - 2005/7/14/entrez SP - 653 EP - 65 JF - Journal of neuroscience research JO - J Neurosci Res VL - 81 IS - 5 N2 - 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-alpha 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 ERalpha antagonist, MPP dihydrochloride, only partially blocked the effects of estrogen, suggesting that estrogen protection was mediated via both ERalpha and ERbeta. LPS treatment did not change ERalpha mRNA levels in microglia, astrocytes, and neurons, but it up-regulated ERbeta mRNA levels in microglia and astrocytes. Similarly, increased ERbeta protein levels were detected in LPS-activated microglia. More interesting was that immunocytochemical analysis revealed that ERbeta 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 ERalpha and ERbeta activation. The cytoplasm location of microglial ERbeta suggests the possible involvement of nonclassical effects of estrogen on microglia. Changes in microglial ERbeta expression levels may modulate such effects of estrogen. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/16013043/Estrogen_provides_neuroprotection_against_activated_microglia_induced_dopaminergic_neuronal_injury_through_both_estrogen_receptor_alpha_and_estrogen_receptor_beta_in_microglia_ L2 - https://doi.org/10.1002/jnr.20583 DB - PRIME DP - Unbound Medicine ER -