Department of Evolutionary and Functional Biology, University of Parma, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Aug 1;35(6):1461-71. doi: 10.1016/j.pnpbp.2010.11.016. Epub 2010 Nov 17.
Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders.
应激性生活事件的暴露与神经精神疾病(如重度抑郁症)的易感性密切相关。临床前动物模型提供了一种有效的工具,可以分离潜在的分子机制。特别是 129SvEv 品系常用于开发转基因小鼠模型,但就行为和神经内分泌功能而言,其特征描述很差。在这里,我们全面描述了 129SvEv 雄性小鼠对社会应激引起的抑郁症样疾病和生理共病的易感性。我们采用了一种经过充分特征描述的慢性社会应激小鼠模型,基于社会挫败和从属。从属 129SvEv 小鼠表现出体重增加、多食、脂肪垫重量增加和基础血浆皮质酮升高。笼内表型揭示了自发运动活性的抑制和短暂性体温升高。从属 129SvEv 小鼠还表现出明显的恐惧、对新的但美味的食物的快感缺失反应、在高架十字迷宫中焦虑增加以及对陌生雄性小鼠的社交回避。生活环境应激程度的直接测量效应,即每天接受的攻击次数,预测了皮质酮水平和运动活性的程度,但不能预测其他参数。这是首次在 129SvEv 雄性小鼠中验证慢性从属应激范式。结果表明,这种小鼠品系具有显著的应激易感性,并确立了将其用作抑郁症样疾病模型的有效性。