产前应激子代大鼠海马Wnt/β-catenin信号通路的改变诱导抑郁和焦虑样行为

Changes of Wnt/β-catenin signaling pathway in the hippocampus caused by prenatal stress induce depression-and anxiety-like behaviors in rats

目的探索海马Wnt/β-catenin信号通路的改变在产前应激(PS)子代大鼠抑郁和焦虑样行为中的作用。方法通过大鼠产前束缚应激建立抑郁模型,将体质量240～260 g的Sprague-Dawley雌鼠随机分成2组,对照组于孕期不做任何处理,产前束缚应激组于孕14～20 d给予束缚应激,3次/d,45 min/次。1月龄子代大鼠随机分为2组:对照组和产前应激组进行实验研究。采用旷场实验(OFT)和强迫游泳实验(FST)评价各组大鼠的抑郁和焦虑样行为,通过Western blot测定各组大鼠海马区Wnt1、Gsk-3β,β-catenin蛋白的表达。结果与对照组相比,产前应激组子代大鼠在旷场实验中的穿越中央格次数明显减少(P<0.01),中央格停留时间显著减少(P<0.05),在强迫游泳实验中不动时间明显延长(P<0.01),表现出明显的焦虑和抑郁样行为。PS使大鼠子代海马Gsk-3β表达显著增加(P<0.01),使β-catenin和Wnt1表达明显降低(P<0.01)。结论产前应激导致Wnt/β-catenin信号系统功能改变,可能引起子代大鼠抑郁和焦虑样行为的产生。

Objective To explore the pathogenic role of changes of Wnt/β-catenin signaling pathway in the hippocampus in depression- and anxiety-like behaviors caused by prenatal stress (PS) in offspring rats. Methods Twelve female Sprague- Dawley rats weighing 240-260 g were randomly divided into control and restraint stress groups. The rats in the control group received no interventions, and those in restraint stress group were subjected to restraint stress (three times a day, 45 min each time) at the gestational age of 14-20 days. The 1-month-old offspring rats underwent open field test and forced swimming test to assess the anxiety- and depression-like behaviors, and the expressions of Wnt1, Gsk-3β and β-catenin in the hippocampus were detected using Western blotting. Results In open field test, the offspring rats with PS showed significantly decreased crossings of the center (P<0.01) with reduced time spent in the center (P<0.05) compared with control offspring rats. In forced swimming test, the offspring rats in PS group exhibited a significantly longer immobility time than in the control rats, and showed obvious depression- and anxiety-like behaviors. Compared with those in the control offspring rats, Gsk-3β expression increased significantly while the expressions of β-catenin and Wnt1 were significantly lowered in the hippocampus of the offspring rats in PS group (P<0.01). Conclusion PS causes changes in Wnt/β-catenin signaling pathway in the hippocampus to contribute to the occurrence of depression- and anxiety-like behaviors in rats.