Early-life stress affects neuronal plasticity of the brain regions participating in the implementation of social behavior. Our previous studies have shown that brief and prolonged separation of pups from their mothers leads to enhanced social behavior in adult female mice. The goal of the present study was to characterize the expression of genes (which are engaged in synaptic plasticity) Egr1, Npas4, Arc, and Homer1 in the prefrontal cortex and dorsal hippocampus of adult female mice with a history of early-life stress. In addition, we evaluated the expression of stress-related genes: glucocorticoid and mineralocorticoid receptors (Nr3c1 and Nr3c2) and Nr1d1, which encodes a transcription factor (also known as REVERBα) modulating sociability and anxiety-related behavior. C57Bl/6 mice were exposed to either maternal separation (MS, 3 h once a day) or handling (HD, 15 min once a day) on postnatal days 2 through 14. In adulthood, the behavior of female mice was analyzed by some behavioral tests, and on the day after the testing of social behavior, we measured the gene expression. We found increased Npas4 expression only in the prefrontal cortex and higher Nr1d1 expression in both the prefrontal cortex and dorsal hippocampus of adult female mice with a history of MS. The expression of the studied genes did not change in HD female mice. The expression of stress-related genes Nr3c1 and Nr3c2 was unaltered in both groups. We propose that the upregulation of Npas4 and Nr1d1 in females with a history of early-life stress and the corresponding enhancement of social behavior may be regarded as an adaptation mechanism reversing possible aberrations caused by early-life stress.

中文翻译：

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生命早期的母亲分离改变了成年雌性小鼠中Npas4和Nr1d1基因的表达：与社会行为的相关性

早期生活压力会影响参与社会行为实施的大脑区域的神经元可塑性。我们以前的研究表明，幼犬与母亲的短暂而长期的分离会导致成年雌性小鼠的社交行为增强。本研究的目的是表征成年雌性小鼠的前额叶皮层和背侧海马中具有早期应激史的基因（参与突触可塑性）Egr1，Npas4，Arc和Homer1的表达。此外，我们评估了压力相关基因的表达：糖皮质激素和盐皮质激素受体（Nr3c1和Nr3c2）和Nr1d1，它编码一种调节社交性和焦虑相关行为的转录因子（也称为REVERBα）。在出生后第2至14天，将C57Bl / 6小鼠暴露于母体分离（MS，每天3小时一次）或进行处理（HD，每天15分钟一次），在成年期，通过某些行为分析雌性小鼠的行为测试，在进行社交行为测试的第二天，我们测量了基因表达。我们发现，成年雌性小鼠具有MS病史，仅在前额叶皮层中增加了Npas4表达，而在额叶皮层和背侧海马中都显示了较高的Nr1d1表达。在HD雌性小鼠中，所研究基因的表达没有改变。压力相关基因Nr3c1和两组中Nr3c2均未改变。我们建议具有早年应激史的女性中Npas4和Nr1d1的上调以及相应的社会行为的增强可以被认为是逆转由早年应激引起的可能畸变的适应机制。