Estrogen provides neuroprotection against activated microglia‐induced dopaminergic neuronal injury through both estrogen receptor‐α and estrogen receptor‐β in microglia

Journal of Neuroscience Research - Tập 81 Số 5 - Trang 653-665 - 2005
Xuan Liu1, Xiao‐Lan Fan1, Yan Zhao1, Guangrui Luo1, Xu‐Ping Li1, Rui Li2,1, Weidong Le1
1Joint Laboratory of Institute of Biomedical Sciences, RuiJin Hospital, Shanghai Second Medical University, and Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Second Medical University, Shanghai, People's Republic of China
2Department of Neurology, Shanxi Provincial People's Hospital, Xi'an, People's Republic of China

Tóm tắt

AbstractEstrogen 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‐α 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 ERα antagonist, MPP dihydrochloride, only partially blocked the effects of estrogen, suggesting that estrogen protection was mediated via both ERα and ERβ. LPS treatment did not change ERα mRNA levels in microglia, astrocytes, and neurons, but it up‐regulated ERβ mRNA levels in microglia and astrocytes. Similarly, increased ERβ protein levels were detected in LPS‐activated microglia. More interesting was that immunocytochemical analysis revealed that ERβ 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 ERα and ERβ activation. The cytoplasm location of microglial ERβ suggests the possible involvement of nonclassical effects of estrogen on microglia. Changes in microglial ERβ expression levels may modulate such effects of estrogen. © 2005 Wiley‐Liss, Inc.

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Tài liệu tham khảo

10.1002/jnr.20017

10.1210/en.2004-0619

10.1212/WNL.53.1.91

10.1210/endo.141.10.7693

10.1002/syn.1067

10.1210/edrv.20.3.0370

10.1016/j.psyneuen.2004.03.008

10.1001/archneur.61.6.886

10.1186/1471-2202-3-6

Dluzen D, 2003, Estrogen as neuroprotectant of nigrostriatal dopaminergic system: laboratory and clinical studies, Endocrinology, 21, 67

10.1046/j.1471-4159.2002.00928.x

10.1002/cne.10325

10.1523/JNEUROSCI.06-08-02163.1986

10.1097/00001756-200002070-00024

10.1016/S0304-3940(96)12937-2

10.1523/JNEUROSCI.20-16-06309.2000

10.2741/1070

10.1523/JNEUROSCI.21-21-08447.2001

10.1016/S0306-4522(03)00245-8

10.1152/jappl.2001.91.4.1860

10.1210/me.2002-0206

10.1124/jpet.102.035048

10.1038/nrm1009

10.1212/WNL.50.4.1141

10.1210/rp.57.1.357

McGeer PL, 2004, Inflammation and neurodegeneration in Parkinson's disease, Parkinsonism Rel Disord, 10, S3, 10.1016/j.parkreldis.2004.01.005

10.1093/jac/48.3.397

10.1002/(SICI)1097-4695(19990915)40:4<484::AID-NEU6>3.0.CO;2-C

10.1016/S0006-8993(02)03475-3

10.1016/j.neulet.2003.10.064

10.1262/jrd.49.275

10.1126/science.277.5331.1508

10.1002/jnr.10833

10.1210/me.2004-0115

10.1016/S0197-4580(88)80079-4

Sawada H, 2003, Estrogens and Parkinson disease: novel approach for neuroprotection, Endocrinology, 21, 77

10.1096/fasebj.14.9.1202

10.1016/S0028-3908(02)00049-7

10.1097/00002826-199903000-00005

10.1210/en.143.3.941

10.1007/s00441-004-0944-0

10.1212/WNL.54.12.2292

10.1523/JNEUROSCI.21-06-01809.2001

10.1073/pnas.1531957100

10.1073/pnas.041617498

10.1016/j.psyneuen.2003.08.010

Women's Health Initiative, 2002, Risks and benefits of estrogen plus progestin in healthy postmenopausal women, JAMA, 288, 1

10.1136/jnnp.2003.020982

10.1073/pnas.0306948101

10.1016/S0006-8993(02)02460-5

10.1111/j.1471-4159.2004.02388.x

10.1074/jbc.M205664200

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Thông tin xuất bản

Journal of Neuroscience Research

Tập 81 Số 5

653-665

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