Effect of donepezil on the proliferation of neurons in subventricular zone and the mechanism of Src signaling pathway in mice with cerebral ischemia
10.3760/cma.j.issn.1674-6554.2017.10.012
- VernacularTitle:多奈哌齐对脑缺血小鼠室管膜下区神经细胞增殖的影响及其Src信号通路机制研究
- Author:
Jianping WANG
1
;
Jiang MAN
;
Xiaojie FU
;
Di ZHANG
;
Zhengfang LU
;
Lie YU
;
Yufeng GAO
;
Xianliang LIU
Author Information
1. 郑州大学第五附属医院神经内科
- Keywords:
Src;
Subventricular zone;
Cerebral ischemia;
Neurogenesis;
Mice;
Donepezil
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2017;26(10):922-926
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of Src signaling pathway in neurogenesis promoted by choline acetyltransferase (CHAT) + neurons in the subventricular zone (SVZ) after ischemic stroke.Methods The eighty-four mice were randomly assigned into four groups:sham-operated mice treated with vehicle (Sham+vehicle,n=18),middle cerebral artery occlusion (MCAO)-operated mice treated with vehicle (MCAO+vehicle,n=22),MCAO mice treated with donepezil (MCAO+donepezil,n=21),MCAO mice treated with donepezil and Src inhibitor KX2-391 (MCAO+donepezil+KX2-391,n=23).Mice were subjected to the temporary MCAO model of ischemic stroke.Modified neurological severity score (mNSS) was used to assess neurologic function of the mice.Proliferative cells were labeled with Ki67,and neuroblasts with doublecortin (DCX).The expression of Ki67+/DCX+ in the SVZ was detected by immunofluorescence.The expression of Ki67,phospho-epidermal growth factor receptor (p-EGFR),p-Raf,Src and p-Akt in the SVZ were quantified by Western blot.Results MCAO+donepezil+KX2-391 group showed worse performance in the mNSS test than MCAO+donepezil group (P＜0.05).Ten days after MCAO,the number of Ki67+/DCX+ cells in the SVZ of MCAO+donepezil group was 125.33± 13.71/area,which was 71.67± 18.35/area in MCAO+ donepezil+KX2-391 group (P＜0.05).What's more,the expression of proteins Ki67,p-EGFR,p-Raf,Src and p-Akt in mice of MCAO+donepezil group was markedly increased,which was (1.39±0.23),(1.42±0.19),(0.88±0.13),(1.14±0.19),(1.04±0.18) and it was decreased in MCAO+donepezil+KX2-391 group,which was 0.84±0.26,0.94±0.26,0.73±0.15,0.71±0.18,0.81±0.19(P＜0.05).Conclusion CHAT+ neurons in SVZ may promote neurogenesis after stroke via Src-epidermal growth factor receptor (EGFR) signaling pathway.
