Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Neurosurgery, Second Affiliated Hospital of Hunan Normal University, Changsha, China.
Behav Brain Funct. 2018 May 15;14(1):10. doi: 10.1186/s12993-018-0142-y.
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.
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).
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.
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.
不良的早期生活经历被认为是神经发育障碍的一个关键因素，这些经历会影响大脑发育、认知能力和心理健康。先前的研究表明，钙结合蛋白 calretinin（CALR）和 calbindin-D28k（CALB）在海马中的水平会因母体剥夺（MD）而发生变化，MD 是一种不良早期生活经历的模型。我们研究了 MD 对海马 CALR 和 CALB 蛋白水平以及认知行为的影响，并探讨了这些影响是否与性别有关。
从出生后第 2 天（PND-2）到第 14 天（PND-14），MD 组的幼鼠与正常饲养的幼鼠（对照组）相比，每天与母亲分离 3 小时。为了确定海马 CALR 和 CALB 水平，在不同时间点（PND-21、-25、-30、-35 和-40）使用海马切片的荧光免疫染色和海马组织的 Western blot 分析。通过旷场试验（PND-21）和 Morris 水迷宫（PND-25）测定行为和认知变化。
Western blot 分析显示，与对照组相比，雄性和雌性 MD 组的海马 CALR 和 CALB 水平均发生了变化。旷场试验仅显示雄性 MD 组的探索减少，但雌性 MD 组没有。Morris 水迷宫测试表明，MD 导致雄性和雌性大鼠的空间记忆受损，但 CALR 和 CALB 水平存在性别差异。
雄性大鼠比雌性大鼠更容易受到 MD 应激的影响，但雄性和雌性大鼠在暴露于 MD 应激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。
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