锂对脆性X综合征小鼠模型的跳台行为及糖原合成酶激酶3β活性的影响  

The effects of lithium on memory ability and glycogen synthase kinase-3β activity in mouse model of fragile X syndrome

作　　者：杨泉[1] 曹开谊[1] 张伟雯[2] 黄越玲[3] 刘国彬[1] 沈岩松[1] 孙卫文[1] 李敏雄[1] 戴丽军[1] 陈盛强[1] 

机构地区：[1]广州医学院第二附属医院神经科学研究所,广州510260 [2]广州医学院第三附属医院,广州510150 [3]广州医学院动物实验中心,广州510182

出　　处：《广东医学》2011年第14期1789-1792,共4页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(编号:30870876);广东省自然科学基金资助项目(编号:815101700100005);广东省科技计划项目(编号:2008B030301371);广州市医药卫生科技一般引导项目(编号:2009-YB-167)

摘　　要：目的探讨氯化锂治疗是否能改善Fmr1基因敲除小鼠(ko鼠)学习跳台行为及糖原合成酶激酶3β(GSK3β)的活性。方法选用30日龄的Fmr1基因敲除小鼠(ko鼠)及同日龄的野生型小鼠(wt鼠),两种小鼠均分别给予生理盐水和氯化锂30、60、90、120、200 mg/kg。观察用药后ko鼠及wt鼠分别在行为学跳台实验中的潜伏期和错误次数。同时用免疫印迹观察ko及wt鼠的海马和皮层的GSK3β和磷酸化GSK3β(P-GSK3β)的表达。结果与未治疗的wt鼠比较,未治疗的ko鼠跳台实验中的潜伏期时间短,错误次数增加,存在学习跳台障碍;免疫印迹实验结果:ko鼠P-GSK3β表达比wt鼠少。氯化锂治疗能够恢复ko鼠的学习跳台行为及增加P-GSK3β的表达量。氯化锂最佳使用剂量为30 mg/kg。结论锂能改善ko鼠的学习跳台能力,可能与锂改善P-GSK3β的表达增加有关,对Fmr1基因敲除小鼠有治疗作用。Objective To evaluate whether lithium ameliorates the learning and memory behavior, and glycogen synthase kinase - 3 β （ GSK3β ） activity in FVB Fmrl gene knockout （ko） mice. Methods The 30 - day - old Fmrl gene ko mice, and wild- type mice （wt mice） were included. Normal saline treatment and lithium treatment of 30, 60, 90, 120 and 200 mg/kg were carried out on both ko and wt mice, respectively. Behavioral latency and error frequencies in step - down passive avoidance test were recorded after treatment. Meanwhile, the expression of GSK3 β and phosphorylated GSK3β （P- GSK3β） in hippocampus and cortex were quantified with Western -blot. Results In mice without treat- ment, shorter behavioral latency, and higher error in step - clown test were revealed in ko mice, when comparing with that of wt mice. Meanwhile, lower expression of P - GSK3 β was observed in ko mice than that in wt mice. These differences were ameliorated by lithium treatment, with maximum efficacy in close of 30 and 60 mg/kg. Conclusion Lithium improves learning and memory ability in ko mice, via up - regulation of P - GSK3 β, providing application in treatment of Fmrl gene ko mice.

关 键 词：脆性X综合征 跳台实验 学习记忆 糖原合成酶激酶3Β 氯化锂 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]