Possible mechanisms of prenatal cold stress induced-anxiety-like behavior depression in offspring rats
Possible mechanisms of prenatal cold stress induced-anxiety-like behavior depression in offspring rats
复制标题
产前冷应激诱发子代大鼠焦虑样行为抑郁的可能机制
DOI：
10.1016/j.bbr.2018.11.008
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发表时间：
2019-02-01
影响因子：
2.7
通讯作者：
Yang, Huanmin
中科院分区：
文献类型：
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作者：
Lim, Shuai;Xu, Bin;Yang, Huanmin
环境因素和产前应激对后代的行为、体格发育、下丘脑-垂体-肾上腺(HPA)轴调节、免疫活动和疾病易感性有长期影响。为进一步了解产前冷应激对仔鼠的影响，我们采用行为测试和生物学分析的方法，观察了仔鼠海马糖皮质激素受体(GR)、盐皮质激素受体(MR)、脑源性神经营养因子(BDNF)、胰岛素样生长因子1受体(IGF1R)、神经元核(Neun)、胶质纤维酸性蛋白(GFAP)、促肾上腺皮质激素释放激素受体1(CRHR1)、γ-氨基丁酸B受体2(GABAB2)蛋白的表达以及外周血中去甲肾上腺素(NE)、多巴胺(DA)水平的变化。结果表明，产前冷应激影响子代HPA轴活性，抑制雄性子代海马区MR、BDNF和IGF1R的表达，降低雌性子代GR的表达。雄性和雌性仔鼠海马区NeuN和GFAP的表达水平也降低，这可能影响了神经元的生长发育。此外，产前冷应激抑制了雄性后代海马区CRHR1和GAB2的表达，导致后代焦虑样行为减少，雄性后代外周血中CD4和CD8淋巴细胞亚群比例降低，后代细胞免疫受到抑制。综上所述，产前冷应激抑制了断奶仔鼠海马神经元的生长发育，诱导仔鼠类焦虑行为减少。
Environmental factors and prenatal stress have long-term effects on offspring behavior, physical development, hypothalamic-pituitary-adrenal (HPA) axis regulation, immune activity, and disease susceptibility. To further understand the effects of prenatal cold stress on offspring, we investigated the behavior change; the expression of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 receptor (IGF1R), neuronal nuclei (NEUN), glial fibrillary acidic protein (GFAP), corticotropin-releasing hormone receptor 1 (CRHR1), Gamma-aminobutyric acid B receptor, 2 (GABAB2) proteins in hippocampus; the ratio of CD4/CD8 lymphocyte subsets and the level of norepinephrine (NE), dopamine (DA) in the peripheral blood of weaned offspring rats using behavioral tests and biology analysis methods. The results showed that prenatal cold stress affected offspring HPA axis activity, inhibited the expression of MR, BDNF and IGF1R in the hippocampus of male offspring, and lowered the expression of GR in female offspring. The expression levels of NEUN and GFAP in the hippocampus of male and female offspring were also reduced, which may have affected the growth and development of neurons. Moreover, prenatal cold stress inhibited the expression of CRHR1 and GABAB2 in the hippocampus of male offspring, leading to decreased anxiety-like behavior in offspring; a reduced ratio of CD4 and CD8 lymphocyte subsets in the peripheral blood of male offspring; and inhibition of offspring cell immunity. In summary, prenatal cold stress inhibits the growth and development of hippocampal neurons in weaned offspring rats, and induces offspring anxiety-like behavior reduced.