Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha B-crystallin
文献类型：期刊论文
| 作者 | Zhang, XH
|
| 刊名 | NATURE
 |
| 出版日期 | 2013 |
| 卷号 | 494期号:7435页码:90-94 |
| 关键词 | HUMAN-BRAIN INFLAMMATION DISEASE MICROGLIA PATHWAY INNATE MICE |
| ISSN号 | 0028-0836 |
| 通讯作者 | Zhou, JW (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China.,jwzhou@ion.ac.cn |
| 英文摘要 | Chronic neuroinflammation is a common feature of the ageing brain and some neurodegenerative disorders. However, the molecular and cellular mechanisms underlying the regulation of innate immunity in the central nervous system remain elusive. Here we show that the astrocytic dopamine D2 receptor (DRD2) modulates innate immunity through alpha B-crystallin (CRYAB), which is known to suppress neuroinflammation(1,2). We demonstrate that knockout mice lacking Drd2 showed remarkable inflammatory response in multiple central nervous system regions and increased the vulnerability of nigral dopaminergic neurons to neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity(3). Astrocytes null for Drd2 became hyper-responsive to immune stimuli with a marked reduction in the level of CRYAB. Preferential ablation of Drd2 in astrocytes robustly activated astrocytes in the substantia nigra. Gain- or loss-of-function studies showed that CRYAB is critical for DRD2-mediated modulation of innate immune response in astrocytes. Furthermore, treatment of wildtype mice with the selective DRD2 agonist quinpirole increased resistance of the nigral dopaminergic neurons to MPTP through partial suppression of inflammation. Our study indicates that astrocytic DRD2 activation normally suppresses neuroinflammation in the central nervous system through a CRYAB-dependent mechanism, and provides a new strategy for targeting the astrocyte-mediated innate immune response in the central nervous system during ageing and disease. |
| 学科主题 | Science & Technology - Other Topics |
| 收录类别 | SCI |
| 资助信息 | Chinese Academy of Sciences; National Basic Research Program of China [2011CBA00408, 2011CB504102]; Natural Science Foundation of China [31021063, 31123002]; Shanghai Metropolitan Fund for Research and Development |
| 语种 | 英语 |
| 公开日期 | 2013-06-04 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/2528]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Zhang, XH. Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha B-crystallin[J]. NATURE,2013,494(7435):90-94. |
| APA | Zhang, XH.(2013).Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha B-crystallin.NATURE,494(7435),90-94. |
| MLA | Zhang, XH."Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha B-crystallin".NATURE 494.7435(2013):90-94. |
入库方式： OAI收割
来源：上海神经科学研究所
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