Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.
Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Sci Rep. 2017 Aug 17;7(1):8570. doi: 10.1038/s41598-017-06984-5.
Major Depression is a prevalent mental disorder that is characterized by negative mood and reduced motivation, and frequently results in social withdrawal and memory-related deficits. Repeated stressors, such as adverse life events, increase the risk for development of the disorder. Consequently, individual variability in stress response greatly weighs on depression-vulnerability and -resilience. Here, we employed the social defeat-induced persistent stress (SDPS) paradigm to identify depression-prone individuals and to examine the temporal development of depression in the months following exposure to brief defeat stress. Male Wistar rats were socially defeated (5 defeat episodes) and single-housed for a prolonged period of time (~24 weeks). We assessed the emergence of a sustained depressive-like state by repeatedly evaluating social motivation (social approach avoidance) and spatial memory (object place recognition) in SDPS rats during the isolation period. Individual variability in the effects of SDPS yielded two extreme subpopulations: an SDPS-prone group that showed gradual affective and cognitive deterioration in terms of social approach and memory retention, and a SDPS-resilient group that did not develop this phenotype. Notably, in SDPS-prone individuals, the affective deficits preceded later cognitive impairments, providing a novel temporal profile of the development of pathology in this preclinical model of sustained depression.
重度抑郁症是一种常见的精神障碍，其特征为情绪低落和动力减退，常导致社交退缩和与记忆相关的缺陷。反复的应激源，如不良生活事件，会增加该疾病的发病风险。因此，个体对压力的反应差异极大地影响了抑郁的易感性和复原力。在这里，我们采用社交挫败诱导的持续性应激（SDPS）范式来鉴定易患抑郁症的个体，并在短暂的挫败应激后几个月内观察抑郁的发展。雄性 Wistar 大鼠经历了社交挫败（5 次挫败经历）并被单独隔离了很长一段时间（~24 周）。我们通过在隔离期间反复评估 SDPS 大鼠的社交动机（社交接近回避）和空间记忆（物体位置识别），来评估持续性抑郁样状态的出现。SDPS 的影响存在个体差异，产生了两个极端的亚群：SDPS 易感组表现出社交接近和记忆保留方面逐渐出现的情感和认知恶化，而 SDPS 抗性组则没有表现出这种表型。值得注意的是，在 SDPS 易感个体中，情感缺陷先于后期认知障碍，为这种持续性抑郁的临床前模型中病理学的发展提供了一个新的时间特征。
