Early-life stress exposure can confer vulnerability for development of psychiatric illnesses and impaired cognition in adulthood. It is well-known that early-life stress can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis in a sex-dependent manner. Specifically, uniparental rodent models of prolonged disrupted mother-offspring relationships (e.g., maternal separation) have demonstrated greater alterations in stress responsivity in adult males, compared to females. Also, chronic early-life stressors (e.g., limited bedding model) impair cognitive function in males more than females. However, the sex-dependent effects of early-life stress and later-life chronic HPA axis activation on cognition have not been well-characterized. Here, we utilized the biparental California mouse (Peromyscus californicus) to model the early-life adversity of paternal deprivation (PD). Fathers either remained in the nest (biparental care) or were permanently removed (PD) on postnatal day (PND) 1. Adult offspring were exposed to daily handling (control) or chronic variable stress (CVS; three stressors for seven days). Twenty-four hours after the final stressor, the novel object recognition (NOR) task commenced, followed by serum collection for corticosterone (CORT) analysis. Independent of sex or rearing, CVS increased CORT. Exploration during acquisition for the NOR task was increased as a result of CVS and PD. During NOR testing, non-stressed females exhibited greater difference scores (i.e., increased recognition memory), compared to non-stressed males. However, the addition of CVS diminished difference scores in females - an effect not observed in CVS-exposed males. Overall, these data suggest that neonatal paternal experience, sex, and chronic stress contribute to exploratory behavior, cognition, and stress hormone concentrations in a biparental species.

中文翻译：

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父亲剥夺和慢性可变压力对成年加利福尼亚小鼠（Peromyscus californicus）的新物体识别的性别依赖性影响。

生命早期的压力暴露可能使人容易罹患精神疾病，并损害成年后的认知能力。众所周知，早年生活中的压力会以性别相关的方式下丘脑-垂体-肾上腺（HPA）轴失调。具体而言，与母体相比，成年男性中长期破坏母子关系（例如母体分离）的单亲啮齿动物模型表现出更大的应激反应性变化。同样，慢性早期应激源（例如，有限的床上用品模型）对男性的认知功能损害要比对女性的损害更大。然而，尚未明确表征早年应激和晚年慢性HPA轴激活对认知的性别依赖性。这里，我们利用双亲加利福尼亚小鼠（Peromyscus californicus）来模拟父亲剥夺（PD）的早期逆境。父亲要么留在巢中（双亲照顾），要么在产后第1天（PND）永久性移出（PD）。成年后代每天要承受日常处理（对照）或慢性可变压力（CVS；三个压力源，持续7天）。最终应激源后二十四小时，开始进行新的对象识别（NOR）任务，然后收集血清进行皮质酮（CORT）分析。与性别或饲养无关，CVS增加了CORT。由于CVS和PD，在NOR任务的获取过程中的探索有所增加。在NOR测试中，与无压力的男性相比，无压力的女性表现出更大的差异评分（即，增加的识别记忆力）。然而，CVS的添加减少了女性的差异评分-在暴露于CVS的男性中未观察到这种效果。总体而言，这些数据表明，新生儿的父亲的经历，性别和慢性压力有助于双亲物种的探索行为，认知和压力激素浓度。