Introduction: Early life stress is a well-described risk factor of anxiety disorders in adulthood. Dysfunction in GABA/glutamate receptors and their functional regulator, calcineurin, is linked to anxiety disorders. Here, we investigated the effect of early life stress, such as repeated maternal separation (MS; 3 h per day from postnatal day [P] 2 to 11), on changes in the expression of calcineurin as well as the ionotropic glutamatergic and GABAergic receptors including α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and GABA_A receptors in the hippocampus and prefrontal cortex (PFC) of adolescent (P35) and adult (P62) male Wistar rats and their correlations with anxiety-like behavior in adulthood. Methods: The protein levels were assessed by Western blot analysis. Anxiety-like behavior was measured in the elevated plus maze (EPM) and open field (OF) tests. Results: MS induced a regional transient decrease of glutamate receptors expression at P35, with decreased NMDA and AMPA receptor levels, respectively, in the hippocampus and PFC, suggesting a possible decrease in excitatory synaptic strength. In contrast to glutamate receptors, MS had long-lasting influence on GABA_A receptor and calcineurin levels, with reduced expression of GABA_A receptor and calcineurin in both brain regions at P35 that continued into adulthood. These results were accompanied by increased anxiety behavior in adulthood, shown by lower percentage of number of total entries and time spent in the open arms of the EPM, and by lower time spent and number of entries in the OF central area. Conclusions: Together, our study suggests that GABA_A receptors via calcineurin-dependent signaling pathways may play an important role in the expression of stress-induced anxiety-like behavior.
Dev Neurosci

中文翻译：

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母体早期分离引起的钙调神经磷酸酶和 GABAA 受体表达的长期下降与成年雄性大鼠焦虑样行为的增加有关

简介：早期生活压力是成年期焦虑症的一个充分描述的危险因素。GABA/谷氨酸受体及其功能调节剂钙调神经磷酸酶的功能障碍与焦虑症有关。在这里，我们研究了早期生活压力的影响，例如反复的母体分离（MS；从出生后一天 [P] 2 到 11 每天 3 小时）对钙调神经磷酸酶以及离子型谷氨酸能和 GABA 能受体表达变化的影响包括青少年 (P35) 海马和前额叶皮层 (PFC) 中的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA)、N-甲基-D-天冬氨酸 (NMDA) 和 GABA _A受体和成年 (P62) 雄性 Wistar 大鼠及其与成年期焦虑样行为的相关性。方法：通过蛋白质印迹分析评估蛋白质水平。在高架十字迷宫 (EPM) 和开放场 (OF) 测试中测量了焦虑样行为。结果： MS 诱导 P35 处谷氨酸受体表达的局部瞬时降低，海马和 PFC 中 NMDA 和 AMPA 受体水平分别降低，表明兴奋性突触强度可能降低。相比于谷氨酸受体，MS对GABA长效影响_甲受体和钙调磷酸酶水平，与GABA的表达降低_甲受体和钙调神经磷酸酶在 P35 的两个大脑区域中持续到成年。这些结果伴随着成年期焦虑行为的增加，表现为在 EPM 的张开臂中花费的总条目数和时间的百分比较低，以及在 OF 中央区域花费的时间和条目数较少。结论：总的来说，我们的研究表明 GABA _A受体通过钙调神经磷酸酶依赖性信号通路可能在压力诱导的焦虑样行为的表达中发挥重要作用。
开发神经科学