Chronic Postnatal Stress Induces Depressive-like Behavior in Male Mice and Programs second-Hit Stress-Induced Gene Expression Patterns of OxtR and AvpR1a in Adulthood
Chronic Postnatal Stress Induces Depressive-like Behavior in Male Mice and Programs second-Hit Stress-Induced Gene Expression Patterns of OxtR and AvpR1a in Adulthood
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DOI：
10.1007/s12035-016-0043-8
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发表时间：
2017-08-01
影响因子：
5.1
通讯作者：
Bock, Joerg
中科院分区：
文献类型：
--
作者：
Lesse, Alexandra;Rether, Kathy;Bock, Joerg
生命早期的慢性压力（CS）是导致包括抑郁症在内的精神障碍发展的主要风险因素。根据双重/多重打击假说，神经精神疾病的病因通常涉及在生命的不同阶段经历的多重压力源。然而，调控多重应激引起的神经元和行为变化的分子和细胞机制尚不清楚。由于催产素能和血管加压能系统是参与环境驱动的应激敏感性适应的神经内分泌调节剂，我们假设出生后的CS程序催产素能和血管加压能受体的表达在青年期第二次应激暴露时发生变化。首先，我们研究了出生后的CS（母亲分离+社会隔离）是否会诱发抑郁样行为，并改变雄性小鼠海马（HC）中催产素受体（OxtR）和精氨酸抗利尿激素受体1a型（AvpR1a）基因表达；(2)成年早期的第二个单一应激源（强迫游泳，FS）是否会影响成年后依赖于CS前经验的OxtR和AvpR1a基因表达。我们发现，出生后的CS诱导了成年早期HC的抑郁样行为和增强的AvpR1a表达。此外，根据我们的假设，只有联合应激暴露（CS + FS），而不是单独的CS或FS，导致成年期HC中OxtR基因表达增加。相比之下，AvpR1a在成年FS和CS + FS动物中的表达均降低。总的来说，我们的结果提供了证据，证明CS控制神经内分泌系统，从而影响晚年的应激反应。
Chronic stress (CS) during early life represents a major risk factor for the development of mental disorders, including depression. According to the Two/Multiple-Hit hypothesis, the etiology of neuropsychiatric disorders usually involves multiple stressors experienced subsequently during different phases of life. However, the molecular and cellular mechanisms modulating neuronal and behavioral changes induced by multiple stress experiences are just poorly understood. Since the oxytocinergic and vasopressinergic systems are neuroendocrine modulators involved in environmentally driven adaptations of stress sensitivity we hypothesized that postnatal CS programs oxytocinergic and vasopressinergic receptor expression changes in response to a second stress exposure in young adulthood. First we investigated if postnatal CS (maternal separation + social isolation) induces depressive-like behavior and alters oxytocin receptor (OxtR) and arginine vasopressin receptor type 1a (AvpR1a) gene expression in the hippocampus (HC) of male mice and (2) if a second single stressor (forced swimming, FS) in young adulthood affects gene expression of OxtR and AvpR1a at adulthood dependent on CS pre-experience. We found that postnatal CS induced depressive-like behavior and enhanced AvpR1a expression in HC at young adulthood. Moreover, in line with our hypothesis, only combined stress exposure (CS + FS), but not CS or FS alone, resulted in increased gene expression of OxtR in HC at adulthood. In contrast, AvpR1a expression was decreased in both adult FS and CS + FS animals. Overall, our results provide evidence that CS programs neuroendocrine systems and thereby influences stress responses in later life periods.