Mechanism research of calcium/calmodulin-dependent serine protein kinase in epileptic seizure in rat models of epilepsy
10.3760/cma.j.issn.1671-8925.2015.06.011
- VernacularTitle:CASK在癫痫大鼠模型中影响癫痫发作的机制研究
- Author:
Zhen LIU
1
;
Yan ZHOU
;
Yi YANG
;
Yuanyuan DANG
;
Yiwu DAI
Author Information
1. 中国人民解放军第三军医大学研究生管理大队
- Keywords:
Calcium/calmodulin-dependent serine protein kinase;
NMDAR2b;
Epilepsy;
Synapse;
Lentivirus
- From:
Chinese Journal of Neuromedicine
2015;14(6):591-596
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the calcium/calmodulin-dependent serine protein kinase (CASK) expression in the hippocampus of epileptic rat models and its mechanism.Methods Thirty healthy adult male Sprague-Dawley rats were randomly divided into 6 groups (n=5):control group and experimental groups of 1,3,7,14 and 30 d after kindling by lithium chloride-pilocarpine;CASK expressions in the hippocampus tissues were measured by immunohistochemistry,immunoflurescence and Western blotting.Another 21 healthy adult male Sprague-Dawley rats were divided into 3 groups (n=7):transfected group,empty adenoviral group and control group,and after anesthesia with chloral hydrate,the same volume of CASK-RNAi-LV,LV-scrRNAi and normal saline was given,respectively;the behavior changes of rats in the three groups were observed within one h of kindling;the expression of N-methel-D-aspartate receptor subunit 2b (NMDAR2b,the downstream of CASK complex),in the transfected group and control group was further examined by Western blotting.Results CASK expressed only in neurons not gliacyte;and the number of CASK positive cells in experimental groups was larger than that in the control group.CASK expression in the hippocampus reduced to minimum level one d after kindling,and maintained at increased levels until 30 days.Both seizure frequency and seizure grade of the epilepsy in the transfected group were significantly decreased as compared with those in the empty adenoviral group and control group (P＜0.05).NMDAR2b expression in the hippocampus of control group increased at the first 24 h of kindling and maintained for 3 days,and then,it decreased 10 days after kindling;NMDAR2b expression in the hippocampus of transfected group was significantly reduced as compared with that in the control group at all time points of kindling (P＜0.05).Conclusions The CASK expression of epilepsy rat models is increased,which influences the occurrence and development of epilepsy.CASK is linked to epilepsy via its action on synaptic NMDAR2b,which may be the potential target of anti-epileptic drugs.
