Thrombin-induced microglial activation contributes to the degeneration of nigral dopaminergic neurons in vivo

被引：19

作者：

Huang C.-F. ^{[1
]}

Li G. ^{[1
]}

Ma R. ^{[2
]}

Sun S.-G. ^{[1
]}

Chen J.-G. ^{[2
]}

机构：

[1] Department of Neurology, Union Hospital, Huazhong University of Science and Technology

[2] Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology

来源：

Neuroscience Bulletin | 2008年 / 24卷 / 2期

基金：

中国国家自然科学基金;

关键词：

Dopaminergic neuron; Microglia; NO; Parkinson's disease; Thrombin;

D O I：

10.1007/s12264-008-0066-x

中图分类号：

学科分类号：

摘要：

Objective: To evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo. Methods: After stereotaxic thrombin injection into unilateral SN of rats, immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and biochemical methods were used to observe tyrosine hydroxylase (TH) immunoreactive positive cells, microglia activation, nitric oxide (NO) amount and inducible nitric-oxide synthase (iNOS) expression. Results: (1) Selective damage to dopaminergic neurons was produced after thrombin injection, which was evidenced by loss of TH immunostaining in time-dependent manner; (2) Strong microglial activation was observed in the SN; (3) RT-PCR demonstrated the early and transient expression of neurotoxic factors iNOS mRNA in the SN. Immunofluorescence results found that thrombin induced expression of iNOS in microglia. The NO production in the thrombin-injected rats was significantly higher than that of controls (P < 0.05). Conclusion: Thrombin intranigral injection can injure the dopaminergic neurons in the SN. Thrombin-induced microglia activation precedes dopaminergic neuron degeneration, which suggest that activation of microglia and release of NO may play important roles in dopaminergic neuronal death in the SN. © 2008 Shanghai Institutes for Biological Sciences, CAS and Springer-Verlag GmbH.

引用

页码：66 / 72

页数：6

共 15 条

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