摘要
目的:探讨聚肌苷酸胞苷酸(polyinosinic-polycytidylic acid,poly I:C)诱导的妊娠母体免疫刺激和出生后母婴分离双重因素对子代精神分裂症样行为的影响及其机制。方法:于母鼠妊娠第17天时尾静脉注射poly I:C(5 mg/kg)或无菌生理盐水,子代小鼠出生后每窝随机选取一半进行母婴分离,另一半不分离。子代鼠出生第21天断奶分笼,第60天进行行为学实验:开场实验、高架十字迷宫实验、新物体/位置识别实验以及水迷宫实验。行为实验结束后,处死小鼠取海马组织,采用蛋白质印迹法检测髓鞘碱性蛋白(myelin basic protein,MBP)的表达。结果:高架十字迷宫实验结果显示,poly I:C可导致雄性小鼠出现抗焦虑;新物体识别实验显示,poly I:C可影响雌子代的认知功能;水迷宫实验结果显示poly I:C对雌、雄仔鼠的学习记忆能力有不同程度的影响,雌性仔鼠颠倒学习能力受损;此外,poly I:C导致雌、雄仔鼠海马MBP降低。母婴分离导致雌、雄仔鼠的体重增长速度减缓、雌性后代的颠倒学习能力降低。结论:poly I:C诱导的母体免疫刺激与母婴分离,均能诱导子代出现精神分裂症样行为表现,且对雌、雄子代的影响不尽相同,两种干预因素没有出现协同或拮抗作用;此外,poly I:C导致了子代的海马髓鞘损伤。
Objective： To figu re out how prenatal immune challenge by polyinosinic-polycytidylic acid （poly I ： C） and maternal derivation affect offsprings in schizophrenia-like behavior and its mechanism. Methods： Pregnant dams were injected with poly I ; C （5 mg/kg） in caudal vein on gestational day 17 （GD17 ） . Pups from the same litter were divided into maternal deprivation （ MD） groups or maternal care （MC） groups randomly. On postnatal day 21, pups were weaned. When they grew up to adults, behavior tests including open field, elevated plus maze, novel object/place recognition, water maze were con-ducted. After all the behavior tests, all pups were killed and their hippocampus were isolated for later use. The expression of myelin basic protein（MBP） were detected by Western blotting. Results： Poly I ： C induced to anti-anxiety behavior in male pups in elevated plus maze,also affected cognitive function in female ones in novel object recognition. Poly I ：C decreased learning and memory ability of female and male pups to varying degrees. Female ones were shown to have reversal learning impairment in poly I ： C group, poly I ： C reduced MBP of hippocampus. The body weight of MD group was much less than MC group. Reversal learning ability was reduced in female pups in MD group. Conclusion ： There is no interaction between the effects of maternal deprivation and prenatal immune challenge by poly I： C. Each of the two factors contributes to schizophrenia-related behavior in female or male pups differently. In addition, prenatal immune challenge by poly I ： C leads to pups, myelin sheath injury in hippocampus.
出处
《江苏大学学报（医学版）》
CAS
2017年第5期379-384,390,共7页
Journal of Jiangsu University：Medicine Edition
基金
国家自然科学基金资助项目(81671053)
江苏省临床医学专项(BL2014068
BE2016724)
江苏大学高级人才科研启动项目(13JDG001
11JDG112)
关键词
精神分裂症动物模型
poly
I:C
妊娠
母婴分离
髓鞘碱性蛋白
animal model of schizophrenia
prenatal immune challenge of poly I： C
maternal depri-vation
myelin basic protein
