摘要
目的 探讨喹硫平（Quetiapine,QUE）对铜离子螯合剂双环己酮草酰二腙（Cuprizone,CPZ）诱导的C57BL/6小鼠精神分裂症模型记忆功能及海马双皮质素（Doublecortin,DCX）表达的影响.方法 48只C57BL/6小鼠按随机数字表法分为对照组（sham）、模型组（CPZ）及药物干预组（CPZ＋QUE）,每组16只.sham组给予普通饲料,CPZ组及CPZ＋QUE组小鼠饲喂含0.2％ CPZ的饲料造模.同时,在CPZ＋QUE组饮水中添加1％二甲基亚砜（DMSO）溶液溶解的QUE（10mg· kg-1·d-1）,sham组与CPZ组接受1％ DMSO溶液作为对照,模型制备及药物干预持续6周.采用Y-迷宫测试观察各组小鼠空间工作记忆能力;免疫荧光染色观察海马DCX阳性新生神经元数量的变化;RT-PCR技术检测海马Notch1、Hes1含量.结果 （1）Y-迷宫实验：CPZ组正确转换率[（22.70±6.70）％]与sham组[（57.69±6.70）％]比较显著降低（P＜0.05）,CPZ组表现出明显的空间工作记忆损害;CPZ＋QUE组的正确转换率为（54.69± 10.06）％,显著高于CPZ组,差异具有统计学意义（P＜0.01）.（2）免疫荧光染色：与sham组比较,CPZ组小鼠海马DCX阳性细胞数量显著降低[（6342.85±1801.72） vs （19428.57±2507.13）,P＜0.01],QUE干预则逆转了这一改变[CPZ＋QUE组vs CPZ组,（15928.57±2049.97）vs（6342.85± 1801.72）,P＜0.01].（3）RT-PCR：CPZ＋QUE组与CPZ组比较,Notch1[（0.97±0.29） vs （0.23±0.20）,P＜0.01]和Hes1[（1.00±0.41） vs （0.38±0.30）,P＜0.01]的mRNA表达量升高,差异有统计学意义（P＜0.01）,与sham组比较,差异无统计学意义（P＞0.05）.结论 喹硫平缓解了CPZ对小鼠海马DCX表达的影响,改善了小鼠的认知功能;喹硫平的上述作用可能是通过激活Notchl信号通路来实现的.
Objective To investigate the effect of quetiapine （QUE） on the memory and doublecortin （DCX） expression in the hippocampus of C57BL/6 mice with cuprizone （CPZ）-induced schizophrenia in C57BL/ 6 mice.Methods 1% dimethyl sulfoxide （DMSO） was used as a vehicle to dissolve QUE.Three group of mice,16 in each of three groups,were treated with vehicle （control group）,0.2% CPZ alone （CPZ group） or 0.2% CPZ combined with 10 mg· kg^-1 · d^-1 QUE （QUE＋CPZ group） for six weeks,respectively.Spatial working memory was evaluated by Y-type maze test 24 hours after the completion of the treatment period.The number of DCX positivenew neurons was calculated by immunofluorescence staining assay.The expression of Notch1 and Hes1 mRNA were detected by reverse transcription-polymerase chain reaction （RT-PCR） assay.Results （1） Y-maze test：CPZ group achieved a much lower percentage of correct alternation than control group （（22.70±6.70） % vs （57.69 ±6.70）%） in Y-maze test （P〈0.05）.The percentage of correct alternation in CPZ ＋ QUE group （（54.69± 10.06） %） was significantly increased compared with CPZ group （P〈0.01）.CPZ mice exhibited significant spatial working memory impairment.（2） Immunofluorescence staining：the number of DCX-positive cells in the hippocampus of the CPZ group （6342.85± 1801.72） was significantly decreased compared with that in control group （19428.57±2507.13） （P〈0.01）,and it was reversed by QUE intervention （15928.57±2049.97）.（3） RT-PCR：the Notch1 and Hes1 mRNA expression in CPZ group were significant lower than that in sham and CPZ ＋ QUE group,（Notch1 （0.97±0.29） vs （0.23±0.20）,P〈0.01）;Hes1 （1.00±0.41） vs （0.38±0.30）,P〈0.01）,and there was no significant difference between sham group and CPZ ＋ QUE group.Conclusion QUE is helpful to relieve CPZ-induced cognitive impairment and decreases expression of DCX in hippocampal,which may be related with activation of Notch1 pathway.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2015年第11期970-973,共4页
Chinese Journal of Behavioral Medicine and Brain Science
基金
国家自然科学基金项目（81371478,81201041,81401109）
关键词
喹硫平
记忆
精神分裂症
小鼠
海马
双皮质素
Quetiapine
Memory
Schizophrenia
Mouse
Hippocampus
Doublecortin
