College of Veterinary Medicine, Department of Neurobiology, Northwest A&F University, Yangling, China.
College of Basic Medicine, Xi'an Medical University, Xi'an, China.
Bipolar Disord. 2021 Jun;23(4):376-390. doi: 10.1111/bdi.12986. Epub 2020 Oct 15.
As a common model for adverse early experience and depression, maternal separation (MS) is always used to investigate the psychological disease. Despite extensive and strong evidence verified the depression-like state induced by MS, little is known about the specific mechanism of MS. Therefore, the present study aimed to investigate the neurobiology mechanism of the MS-induced depression-like state.
To verify the depression-like behaviors of offspring induced by MS, a series of behavioral tests were performed. Then, in vivo electroporation and three-dimensional reconstruction, combining with immunohistochemistry and BrdU labeling, were mainly used to explore the neurogenesis and synaptogenesis in postnatal dentate gyrus.
Prolonged MS indeed induced the depression-like behaviors of offspring in adulthood. Surprisingly, learning and memory were enhanced by prolonged MS. Further investigation indicated that prolonged MS inhibited the proliferation of neural stem cells, impaired the survival, and altered the fate decision of newborn cells, whereas the total length and terminal tips of dendrite, and the spine density, especially thin spine, were significantly increased in prolonged MS mice.
Our results elucidated that prolonged MS induced the depression-like state by impairing postnatal neurogenesis of dentate gyrus. Importantly, our results emphasized that prolonged MS increased the spine density, especially thin spine, by increasing the total length and number of terminal tips of dendrite, thereby enhancing learning and memory.
作为不良早期经历和抑郁的常见模型，母体分离（MS）常用于研究心理疾病。尽管有大量强有力的证据证实了 MS 引起的类似抑郁的状态，但对 MS 具体的机制知之甚少。因此，本研究旨在探讨 MS 引起的类似抑郁状态的神经生物学机制。
通过一系列行为测试验证 MS 诱导的后代类似抑郁行为。然后，主要采用电穿孔和三维重建，结合免疫组织化学和 BrdU 标记，来探索产后齿状回中的神经发生和突触发生。
长时间的 MS 确实导致了成年后代的类似抑郁行为。令人惊讶的是，长时间的 MS 增强了学习和记忆。进一步的研究表明，长时间的 MS 抑制了神经干细胞的增殖，损害了新生细胞的存活和命运决定，而延长 MS 组的树突总长度和末端分支点以及棘密度，尤其是细棘密度，显著增加。
我们的结果表明，长时间的 MS 通过损害齿状回的产后神经发生引起类似抑郁的状态。重要的是，我们的结果强调，长时间的 MS 通过增加树突总长度和末端分支点的数量来增加棘密度，特别是细棘密度，从而增强学习和记忆。
