BACKGROUND AND OBJECTIVE Adverse early-life experiences have been suggested as one of the key contributors to neurodevelopmental disorders, such that these experiences influence brain development, cognitive ability and mental health. Previous studies indicated that hippocampal levels of the calcium-binding proteins calretinin (CALR) and calbindin-D28k (CALB) changed in response to maternal deprivation (MD), a model for adverse early-life experiences. We investigated the effects of MD on hippocampal CALR and CALB protein levels and cognitive behaviors, and explored whether these effects were sex-related. METHODS From postnatal day 2 (PND-2) to PND-14, rat pups in the MD group were separated from their mothers for 3 h/day for comparison with pups raised normally (control). To determine hippocampal CALR and CALB levels, fluorescent immunostaining of hippocampal sections and Western blot analysis of hippocampal tissues were employed at various timepoints (PND-21, -25, -30, -35 and -40). Behavioral and cognitive changes were determined by open field test (PND-21) and Morris water maze (PND-25). RESULTS Western blot analysis showed changes in the hippocampal CALR and CALB levels in both male and female MD groups, compared with controls. The open field test showed reduced exploration only in male MD groups but not female MD groups. The Morris water maze tests indicated that MD caused spatial memory impairment both in male and female rats, but there was a sex difference in CALR and CALB levels. CONCLUSIONS Male rats are relatively more vulnerable to MD stress than female rats, but both male and female rats demonstrate spatial learning impairment after exposure to MD stress. Sex difference in CALR and CALB levels may reveal the different mechanisms behind the behavioral observations.

中文翻译：

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母体剥夺与海马钙结合蛋白改变与大鼠认知功能之间的关联性别差异。

背景和目的已提出不良的早期生活经历是神经发育障碍的关键因素之一，因此这些经历会影响大脑的发育，认知能力和心理健康。先前的研究表明，钙结合蛋白钙调蛋白（CALR）和钙结合蛋白-D28k（CALB）的海马水平会因不良的早期生活经历模型母体剥夺（MD）而发生变化。我们调查了MD对海马CALR和CALB蛋白水平和认知行为的影响，并探讨了这些影响是否与性别相关。方法从出生后第2天（PND-2）到PND-14，将MD组的幼崽与母亲分开3小时/天，以与正常饲养的幼崽（对照组）进行比较。要确定海马CALR和CALB水平，在不同的时间点（PND-21，-25，-30，-35和-40）采用海马切片的荧光免疫染色和海马组织的蛋白质印迹分析。行为和认知变化通过露天试验（PND-21）和莫里斯水迷宫（PND-25）确定。结果Western blot分析显示，与对照组相比，男性和女性MD组海马CALR和CALB水平均发生了变化。野外试验表明，仅在男性MD组中探索减少，而在女性MD组中则没有。莫里斯水迷宫测试表明，MD引起了雄性和雌性大鼠的空间记忆障碍，但CALR和CALB水平存在性别差异。结论雄性大鼠比雌性大鼠相对更容易遭受MD压力，但是雄性和雌性大鼠在暴露于MD压力后均表现出空间学习障碍。CALR和CALB水平的性别差异可能揭示了行为观察背后的不同机制。