哺乳期短暂的幼仔分离使产后 C57BL/6J 母鼠在慢性束缚应激诱导的行为缺陷中具有恢复力。
Brief pup separation during lactation confers resilience in behavioural deficits induced by chronic restraint stress in postpartum C57BL/6J dams.
机构信息
From the Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China (Zhou, Wu, G. Wang, Xiao, H. Wang, Xie, Sun); the Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Wu); the Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark (Zhao).
From the Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, China (Zhou, Wu, G. Wang, Xiao, H. Wang, Xie, Sun); the Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Wu); the Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark (Zhao)
出版信息
J Psychiatry Neurosci. 2023 May 12;48(3):E154-E170. doi: 10.1503/jpn.220079. Print 2023 May-Jun.
BACKGROUND
The postpartum period is a complex time for females that affects health recovery. Stress during this period is one of the main risk factors for depression. Therefore, preventing stress-induced depression in the postpartum period is of great importance. Pup separation (PS) is a natural paradigm of postpartum care; however, the effect of different PS protocols during lactation on stress-induced depressive behaviours in dams is unknown.
METHODS
Lactating C57BL/6J mice were subjected to no pup separation (NPS), brief PS (15 min/day, PS15) or long PS (180 min/day, PS180) from postpartum day 1 to postpartum day 21 and were then subjected to chronic restraint stress (CRS) for 21 days. Behavioural tests, specifically the open field test (OFT), elevated plus maze (EPM) test and tail suspension test (TST), were performed. The expression of mRNA and protein in the hippocampus and microbiota composition were also assessed.
RESULTS
We observed CRS-induced anxiety- and depression-like behaviours in NPS dams. In addition, in NPS dams, microglial activation and the levels of NOD-like receptor pyrin domain containing 3, caspase-1 and interleukin-1β were increased, whereas expression levels of collapsing response mediator protein 2 (CRMP2) and α-tubulin were decreased. However, immobility time in the TST was lower in PS15+CRS dams than in NPS+CRS dams, and time spent in the centre during the OFT and in the open arms during the EPM test was higher in PS15+CRS dams, indicating resilience. Expression of hippocampal biomarkers of neuroinflammation was inhibited and levels of CRMP2-mediated neuroplasticity were increased in PS15+CRS dams. Notably, we observed taxonomic changes in the cecal microbiota across different PS groups, as well as relationships between gut microbiota composition and some biomarkers of hippocampal neuroinflammation and neuroplasticity.
LIMITATIONS
The sample size for gut microbiota analysis in this study was small.
CONCLUSION
Collectively, the results of this study confirm that brief PS confers stress resilience in CRS-induced behavioural deficits and reverses hippocampal neuroinflammation-neuroplasticity injury and gut microbiota imbalance.
背景
产后时期是女性健康恢复的一个复杂时期。在此期间的压力是导致抑郁的主要风险因素之一。因此，预防产后期间的应激性抑郁非常重要。幼仔分离（PS）是产后护理的自然范例；然而，哺乳期不同 PS 方案对母体应激诱导抑郁行为的影响尚不清楚。
方法
哺乳期 C57BL/6J 小鼠从产后第 1 天至第 21 天分别进行无幼仔分离（NPS）、短暂 PS（15 分钟/天，PS15）或长时间 PS（180 分钟/天，PS180），然后进行 21 天慢性束缚应激（CRS）。进行行为测试，特别是旷场测试（OFT）、高架十字迷宫（EPM）测试和悬尾测试（TST）。还评估了海马体中的 mRNA 和蛋白质表达以及微生物群落组成。
结果
我们观察到 CRS 诱导 NPS 母鼠出现焦虑和抑郁样行为。此外，在 NPS 母鼠中，小胶质细胞激活以及 NOD 样受体含 pyrin 结构域蛋白 3、半胱天冬酶-1 和白细胞介素-1β的水平升高，而 collapsin 反应介质蛋白 2（CRMP2）和α-微管蛋白的表达水平降低。然而，PS15+CRS 母鼠的 TST 不动时间低于 NPS+CRS 母鼠，PS15+CRS 母鼠在 OFT 中的中心时间和 EPM 测试中的开放臂时间更高，表明具有恢复力。PS15+CRS 母鼠的海马神经炎症生物标志物表达受到抑制，CRMP2 介导的神经可塑性水平升高。值得注意的是，我们观察到不同 PS 组之间盲肠微生物群落的分类变化，以及肠道微生物群落组成与海马神经炎症和神经可塑性的一些生物标志物之间的关系。
局限性
本研究中肠道微生物组分析的样本量较小。
结论
总之，这项研究的结果证实，短暂的 PS 可在 CRS 诱导的行为缺陷中赋予应激恢复力，并逆转海马神经炎症-神经可塑性损伤和肠道微生物失衡。
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