GSK3抑制剂氯化锂对脆性X综合征模型小鼠避暗行为的干预作用  

Theraputic effects of lithium chloride on passive avoidance behavior in a mouse model of Fragile X Syndrome

作　　者：陈盛强[1,2] 罗学港 杨泉[1,2] 曹开谊[2] 孙卫文[2] 陈希[2] 张维雯[3] 黄越玲[2] 刘国彬[2] 沈岩松[2] 戴丽军[2] 易咏红[2] 

机构地区：[1]中南大湘雅医学院人体解剖学和神经生物学系,长沙410013 [2]广州医学院第二附属医院 [3]广州医学院第三附属医院

出　　处：《中国神经精神疾病杂志》2012年第8期486-489,共4页Chinese Journal of Nervous and Mental Diseases

基　　金：广东省自然科学基金项目(编号:815101700100005);广东省科技计划项目(编号:2008B030301371;2009B030801368)

摘　　要：目的探讨糖原合成酶激酶3(glycogen synthase kinase3,GSK3)抑制剂氯化锂对脆性X综合症小鼠模型的避暗行为的干预作用及机制。方法通过对30日龄脆性X综合症小鼠连续腹腔注射不同剂量氯化锂5 d,用药第4天和第5天进行避暗实验;同时用免疫印迹技术检测Fmr1 knockout(KO)及wild type(WT)小鼠的海马和皮层总GSK 3β和磷酸化GSK 3β(P-GSK3β)的变化。结果在避暗实验中,KO鼠与WT鼠,两者潜伏期及错误次数分别为(56±32)s,(83±24)s;(7±3)次,(3±2)次;免疫印迹实验结果:KO鼠皮层及海马P-GSK3β表达平均灰度值分别为69,63;WT鼠皮层和海马均为100。注射氯化锂后,KO鼠和WT鼠总GSK3β无明显改变,而KO鼠60 mg/kg,120 mg/kg,200 mg/kg组皮层P-GSK3β表达平均灰度值分别为:147,151,234;海马P-GSK3β分别为108,111,146,较空白组增多;P<0.05。WT鼠用氯化锂后,潜伏期和错误次数以及P-GSK3β表达变化无统计学意义。结论氯化锂能改善KO鼠的学习记忆能力,可能与氯化锂导致的P-GSK3β的表达增加有关,对脆性X综合征基因敲除小鼠有治疗作用。Objective To study the theraputic effects of lithium chloride on step-through behaviors and the activity of Glycogen Synthase Kinase 3β （GSK3β） in Fragile X Syndrome in mice. Methods Thirty-day-oht wild- type （WT） or Fmrl KO littermates received either normal saline or different doses of lithium chloride （30 mg/kg, 60 mg/kg, 90 mg/kg, 120 mg/kg or 200 mg/kg） for five consecutive days. Step-through testing was used to detect the latency period and error c, ount at 4 and 5 days following lithium treatment. Meanwhile, Western blot was used to ex- amine the expression of GSK3β and Phosphorylated GSK3β（P-GSK3β,） in mouse hippocampus and cortex. Results Compared with non-treated WT mice, non-treated KO mice had shorter latency period and more error counts in pas- sive avoidanee tests, suggesting that KO mice had learning and memory impairments. The expression level of phos- phoc,lated P-GSK3β） was lower in Fmrl KO than in WT mice. Lithium treatment could ceover the learning and memory impairments and increase the expression level of P-GSK3. Conclusions Lithium ameliorates passive avoid- ance impairment probably through increasing the expression of P-GSK3βin the Fmrl knockout mice.

关 键 词：脆性X综合症FMR1基因敲除 避暗实验GSK3β 磷酸化GSK3β 氯化锂 

分 类 号：R742.1[医药卫生—神经病学与精神病学]