College of Acupuncture and Massage, College of Regimen and Rehabilitation, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Biomed Res Int. 2021 Jul 29;2021:6681397. doi: 10.1155/2021/6681397. eCollection 2021.
Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.
早期生活压力是导致以后生活中出现抑郁的一个重要决定因素。据报道，母体分离（MS）在再次暴露于应激时可引发成年后的应激敏感性。然而，它也可能导致对应激引起的抑郁产生弹性。这些结论是相互矛盾的。为了解决这个问题，C57BL/6N 新生幼鼠从产后第 1 天（PD1）到第 21 天（PD21）每天接受短暂的 MS（15 分钟/天；MS15）或长时间的 MS（180 分钟/天；MS180）。然后，成年小鼠从 PD64 到 PD105 接受慢性不可预测的轻度应激（CUMS）暴露。在此期间，每周进行一次强迫游泳试验（FST）、悬尾试验（TST）和旷场试验等行为测试。此外，在 PD106 时测量海马神经甾体、血清应激激素和海马单胺神经递质。我们发现，MS180 组的小鼠在 FST 和 TST 中挣扎时间减少，不动时间延长。然而，MS15 组没有明显差异。MS180 组的海马神经甾体（孕酮和别孕烯醇酮）水平降低，血清皮质酮、促肾上腺皮质激素释放激素和促肾上腺皮质激素水平升高。此外，MS180 组的单胺神经递质如 5-羟色胺和 5-羟吲哚乙酸的表达显著降低，但 MS15 组没有。所有发现表明，与短暂 MS 相比，成年期再次暴露于应激时，长时间 MS 会增加出现类似抑郁行为的易感性。然而，需要进一步的研究来确定 MS 经历对成年后应激再暴露易感性的潜在神经分子机制。
