Laboratory of Gene Expression Regulation, Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, Russia.
Laboratory of Molecular Mechanisms of Pathological Processes, Institute of Cytology and Genetics, SB RAS, Novosibirsk, Russia.
Genes Brain Behav. 2020 Mar;19(3):e12541. doi: 10.1111/gbb.12541. Epub 2018 Dec 26.
The hippocampus is a crucial part of the limbic system involved both in cognitive processing and in the regulation of responses to stress. Adverse experiences early in life can disrupt hippocampal development and lead to impairment of the hypothalamic-pituitary-adrenal axis response to subsequent stressors. In our study, two types of early-life stress were used: prolonged separation of pups from their mothers (for 3 hours/day, maternal separation, MS) and brief separation (for 15 minutes/day, handling, HD). In the first part of our study, we found that adult female mice (F0) who had experienced MS showed reduced locomotor activity and impairment of long-term spatial and recognition memory. Analysis of various hippocampal regions showed that MS reduced the number of mature neurons in CA3 of females, which is perhaps a crucial hippocampal region for learning and memory; however, neurogenesis remained unchanged. In the second part, we measured maternal care in female mice with a history of early-life stress (F0) as well as the behavior of their adult offspring (F1). Our results indicated that MS reduced the level of maternal care in adult females (F0) toward their own progeny and caused sex-specific changes in the social behavior of adult offspring (F1). In contrast to MS, HD had no influence on female behavior or hippocampal plasticity. Overall, our results suggest that prolonged MS early in life affects the adult behavior of F0 female mice and hippocampal neuronal plasticity, whereas the mothers' previous experience has effects on the behavior of their F1 offspring through disturbances of mother-infant interactions.
海马体是边缘系统的重要组成部分，参与认知处理和对压力反应的调节。生命早期的不良经历会破坏海马体的发育，并导致下丘脑-垂体-肾上腺轴对随后的应激源的反应受损。在我们的研究中，使用了两种类型的早期生活应激：延长幼仔与母亲的分离（每天 3 小时，母体分离，MS）和短暂分离（每天 15 分钟，处理，HD）。在我们研究的第一部分，我们发现经历 MS 的成年雌性小鼠（F0）的运动活性降低，并且长期空间和识别记忆受损。对各种海马体区域的分析表明，MS 减少了雌性 CA3 中成熟神经元的数量，这可能是学习和记忆的关键海马体区域；然而，神经发生保持不变。在第二部分，我们测量了具有早期生活应激史的雌性小鼠（F0）的母性行为以及其成年后代（F1）的行为。我们的结果表明，MS 降低了成年雌性（F0）对其后代的母性行为，并导致成年后代（F1）的社会行为出现性别特异性变化。与 MS 相反，HD 对雌性行为或海马体可塑性没有影响。总体而言，我们的结果表明，生命早期的长时间 MS 会影响 F0 雌性小鼠的成年行为和海马体神经元可塑性，而母亲的先前经历则通过干扰母婴互动对其 F1 后代的行为产生影响。
