母体妊娠期精神压力暴露对子代鼠脑白质超微机构及其认知功能的影响

Maternal stress exposure during pregnancy impairs ultrastructural changes in the white matter and reduces cognitive function in offspring mice

目的:探究母体妊娠期精神压力暴露对子代鼠认知功能及脑白质超微结构的影响。方法:亲代鼠分为压力束缚暴露组(PE组)和对照组(C组)两组,雌性SD大鼠阴道涂片阳性日期为妊娠第0天。PE组亲代雌鼠妊娠第14~20天暴露于束缚压力(3次/天),持续45 min~1 h/次。1月龄子代鼠行为学测试(Morris水迷宫和Y迷宫),后心脏灌注固定脑标本并置入混合固定液中。使用现代体视学方法计算脑白质总体积、有髓神经纤维总长度及总体积和髓鞘总长度及总体积,对髓鞘内外直径及内外周长进行计分析。结果:(1)行为学测试:与C组相比,PE组小鼠第3、4天Morris水迷宫定位航行试验潜伏期显著延长、空间探索试验平台所在象限滞留时间百分比和穿越平台有效区域次数显著减少,Y迷宫新颖臂探索距离、探索次数及探索时间明显增加(P<0.05)。(2)与C组相比,PE组小鼠脑白质总体积、有髓神经纤维总长度、有髓神经纤维总体积、髓鞘总体积明显下降(P<0.05),髓鞘内直径、外直径明显下降(P<0.05),内周长、外周长及内外周长差明显增加(P<0.05)。(3)行为学测试结果与脑白质超微结构测定结果间存在相关关系。结论:母体妊娠期精神压力暴露可损害子代鼠认知功能及脑白质及其超微结构,认知功能降低与脑白质损害间存在相关关系。

Objective:To explore whether maternal stress exposure during pregnancy impairs cognitive function and white matter ultrastructure in offspring mice.Methods:The parent rats were divided into two groups:the pressure exposure group(group PE)and the control group(group C).The positive date of vaginal smear of female SD rats was day 0 of gestation.Female mice in group PE were exposed to binding pressure(3 times/day)on day 14-20 of gestation for 45 min-1 h/time.Behavioral tests(Morris water maze and Y maze)were performed on 1-month-old offspring mice followed by cardiac perfusion of fixed brain speci-mens and placement in mixed fixative solution.The total volume of white matter,total length and volume of myelinated nerve fi-bers and total length and volume of myelin sheath were calculated using modern stereoscopic methods,and the inner and outer di-ameter and inner and outer circumference of the myelin sheath were analyzed.Results:(1)Behavioral tests:compared with the group C,the average latency of the 3th and 4th day in the group PE were significantly prolonged,the percentage of the resting time in the quadrant of the platform and the frequency of acrossing the effective area of platform in the fifth day of space exploration experiment were significantly reduced of Morris water maze test,and visiting distance,duration and numbers in novel arm significantly increased of Y-maze test(P<0.05).(2)Compared with group C,the total volume of white matter,total length of myelin-ated nerve fibers,total volume of myelinated nerve fibers and myelin sheath in the group PE were significantly reduced(P<0.05),the inner diameter and outer diameter of myelin sheath decreased significantly(P<0.05),and the inner perimeter,outer perimeter and inner and outer perimeter differences increased significantly(P<0.05).(3)There was a correlation between behavioral test results and white matter ultrastructure measurement results.Conclusion:Maternal stress exposure during pregnancy could impair the cognitive function and white matter and its ultrastructure in the offspring,and there was a correlation between de-creased cognitive function and white matter damages.