Abstract
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.
Highlights
A large body of evidence that has accumulated to date indicates that exposure to stressful events early in life affects subsequent development and predisposition to various psychiatric disorders [1, 2]
We found that only the Npas4 mRNA level changed under the influence of early-life stress and only in one brain region: the prefrontal cortex (Fð2, 22Þ = 3:65, p = 0:042)
We demonstrated that the expression of a nuclear receptor gene, Nr1d1, increases both in the dorsal hippocampus and in the prefrontal cortex of female mice with a history of MS
Summary
A large body of evidence that has accumulated to date indicates that exposure to stressful events early in life affects subsequent development and predisposition to various psychiatric disorders [1, 2]. The influence on anxiety is reported to be roughly equal between the sexes, disturbances in memory formation and learning abilities are detected more frequently in males than in females, and this effect is more stable than the effect on females; the directionality is generally comparable between the sexes (see reviews [3, 4]). The most contradictory effects of early-life stress are the effects on social behavior. Some authors have stated that maternal separation results in shorter time investigating a partner in adult [7, 9] or juvenile females [5, 10], while others suggest that maternal separation has no effect on female social behavior [11,12,13]
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