Liu Na, Wang Yulu, An Aerin Y, Banker Christopher, Qian Yi-Hua, O'Donnell James M
Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Department of Traditional Medical Orthopedics, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shanxi, China.
Eur J Neurosci. 2020 Jul;52(1):2694-2704. doi: 10.1111/ejn.14565. Epub 2019 Sep 17.
Single-housed stress elicits a range of social isolation-related behavioral and neurobiological abnormalities. To investigate single housing-induced behavioral changes and sex differences on stress outcomes, we examined single-housed stress-induced learning and memory impairment, depression-like behaviors, neuroplasticity abnormalities and underlying mechanism. The results showed that male and female mice socially isolated for 8 weeks had significantly decreased memory acquisition, as demonstrated in the learning curve of the Morris water maze task. Memory consolidation and retrieval were also decreased in both the single-housed male and female mice. These findings were corroborated further by the two classical animal models, Y-maze and novel object recognition tests, as demonstrated by reduced spontaneous alternation and recognition index in both sexes of single-housed mice. Subsequent studies suggested that single-housed male mice exhibited increased immobility time in both the forced swim and tail suspension tests, while the female mice only exhibited increased immobility time in the tail suspension test. Moreover, single-housed stress significantly decreased the apical and basal branch points, dendritic length, and spine density in the CA1 of hippocampal neurons in both male and female mice. These effects were consistent with decreased neuroplasticity and neuroprotective-related molecules such as synaptophysin, PSD95, PKA, pCREB and BDNF expression. These findings suggest that loss of neuronal remodeling and neuroprotective mechanisms due to single housing are involved in behavioral changes in both male and female mice. The results provide further evidence that neuroplasticity-related signaling plays a crucial role in isolation-induced effects on neuropsychiatric behavioral deficits in both sexes.
单笼饲养应激会引发一系列与社会隔离相关的行为和神经生物学异常。为了研究单笼饲养引起的行为变化以及应激结果中的性别差异，我们检测了单笼饲养应激诱导的学习和记忆损伤、抑郁样行为、神经可塑性异常及其潜在机制。结果显示，在莫里斯水迷宫任务的学习曲线中，社会隔离8周的雄性和雌性小鼠的记忆获取能力显著下降。单笼饲养的雄性和雌性小鼠的记忆巩固和提取能力也有所下降。单笼饲养小鼠两性的自发交替和识别指数降低，这在Y迷宫和新物体识别测试这两种经典动物模型中得到了进一步证实。随后的研究表明，在强迫游泳和悬尾测试中，单笼饲养的雄性小鼠静止不动的时间增加，而雌性小鼠仅在悬尾测试中静止不动的时间增加。此外，单笼饲养应激显著降低了雄性和雌性小鼠海马神经元CA1区的顶枝和基枝分支点、树突长度以及棘密度。这些影响与神经可塑性和神经保护相关分子如突触素、PSD95、PKA、pCREB和BDNF表达的降低一致。这些发现表明，单笼饲养导致的神经元重塑和神经保护机制丧失与雄性和雌性小鼠的行为变化有关。结果进一步证明，神经可塑性相关信号在隔离诱导的两性神经精神行为缺陷中起关键作用。
