Thrombin-induced microglial activation impairs hippocampal neurogenesis and spatial memory ability in mice

Behavioral and Brain Functions

Yuan Yang¹  Meikui Zhang³  Xiaoni Kang³  Chen Jiang³  Huan Zhang²  Pei Wang³  Jingjing Li³ 

[1] Department of Neurological, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100036, China

[2] Department Students Brigade, The Second Military Medical University, No. 800, Xiangyin Road, Shanghai, 200433, China

[3] Department of Telemedicine Center, Chinese PLA General Hospital, No. 28, Fuxing Road, Haidian District, Beijing, 100036, China

关键词: Spatial memory deficit;    Microglia/macrophages;    Doublecortin;    Hirudin;    Intrastriatal hemorrhage;    Neurogenesis;   

Others  :  1227112
DOI  :  10.1186/s12993-015-0075-7

 received in 2015-03-04, accepted in 2015-09-11,  发布年份 2015

【 摘 要 】

Background

To investigate the effects of microglia/macrophages activation induced by intrastriatal thrombin injection on dentate gyrus neurogenesis and spatial memory ability in mice.

Methods

The male C57BL/6 mice were divided into 4 groups of 10: sham, intracerebral hemorrhage (ICH), ICH + hirudin (thrombin inhibitor), and ICH + indometacin (Indo, an anti-inflammation drug). ICH model was created by intrastriatal thrombin (1U) injection. BrdU (50 mg/kg) was administrated on the same day after surgery for 6 consecutive days. Motor functions were evaluated with rotarod and beam walking tests. The spatial memory deficit was measured with Morris water maze (MWM). Cell quantification was performed for doublecortin (DCX, immature neuron), BrdU (S-phase proliferating cell population) and CD68 (activated microglia/macrophage) immune-reactive cells.

Results

Microglia/macrophages activation induced by intrastriatal thrombin injection reduced hippocampal neurogenesis and impaired spatial memory ability, but did not affect the motor function at 3 and 5 days post-injury. Both hirudin and indometacin reduced microglia/macrophages activation, enhanced hippocampal neurogenesis, and improved spatial memory ability in mice.

Conclusions

Microglia/macrophages activation induced by intrastriatal thrombin injection might be responsible for the spatial memory deficit. Targeting both thrombin and inflammation systems in acute phase of ICH might be important in alleviating the significant spatial memory deficits.

【 授权许可】

   
2015 Yang et al.

【 图 表 】

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