Sathyanesan Monica, Haiar Jacob M, Watt Michael J, Newton Samuel S
a Division of Basic Biomedical Sciences , Sanford School of Medicine, University of South Dakota , Vermillion , SD , USA.
Stress. 2017 Mar;20(2):197-204. doi: 10.1080/10253890.2017.1298587. Epub 2017 Mar 8.
The inbred mouse strains, C57BL/6 and BALB/c have been used widely in preclinical psychiatric research. The differences in stress susceptibility of available strains has provided a useful platform to test pharmacological agents and behavioral responses. Previous brain gene profiling efforts have indicated that the inflammation and immune response gene pathway is the predominant gene network in the differential stress response of BALB/c and C57BL/6 mice. The implication is that a composite stress paradigm that includes a sequence of extended, varied and unpredictable stressors induces inflammation-related genes in the hippocampus. We hypothesized that the regulation of inflammation genes in the brain could constitute a primary stress response and tested this by employing a simple stress protocol, repeated exposure to the same stressor for 10 days, 2 h of restraint per day. We examined stress-induced regulation of 13 proinflammatory cytokine genes in male BALB/c and C57BL/6 mice using quantitative PCR. Elevated cytokine genes included tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 10 (IL10), tumor necrosis factor (TNF) super family members and interleukin 1 receptor 1 (IL1R1). In addition, we examined restraint stress-induced regulation of 12 glutamate receptor genes in both strains. Our results show that restraint stress is sufficient to elevate the expression of inflammation-related genes in the hippocampus of both BABLB/c and C57BL/6 mice, but they differ in the genes that are induced and the magnitude of change. Cell types that are involved in this response include endothelial cells and astrocytes. Lay summary Repeated exposure to a simple restraint stress altered the activities of genes involved in inflammation and the functions of the excitatory neurotransmitter, glutamate. These changes in the hippocampus of the mouse brain showed differences that were dependent on the strain of mice and the length of the stress exposure. The effects of stress on activity of these genes may lead to alterations in behavior.
近交系小鼠品系C57BL/6和BALB/c已广泛应用于临床前精神病学研究。现有品系在应激易感性方面的差异为测试药物制剂和行为反应提供了一个有用的平台。先前的脑基因谱分析表明，炎症和免疫反应基因通路是BALB/c和C57BL/6小鼠差异应激反应中的主要基因网络。这意味着一种复合应激范式，即一系列持续时间长、种类多样且不可预测的应激源，会诱导海马体中与炎症相关的基因。我们假设大脑中炎症基因的调节可能构成主要的应激反应，并通过采用一种简单的应激方案进行了测试，即每天对同一应激源进行2小时的束缚，持续10天。我们使用定量PCR检测了雄性BALB/c和C57BL/6小鼠中应激诱导的13种促炎细胞因子基因的调节情况。细胞因子基因升高的包括肿瘤坏死因子α（TNFα）、白细胞介素6（IL6）、白细胞介素10（IL10）、肿瘤坏死因子（TNF）超家族成员和白细胞介素1受体1（IL1R1）。此外，我们检测了两种品系中束缚应激诱导的12种谷氨酸受体基因的调节情况。我们的结果表明，束缚应激足以提高BABLB/c和C57BL/6小鼠海马体中与炎症相关基因的表达，但它们在诱导的基因和变化幅度上存在差异。参与这种反应的细胞类型包括内皮细胞和星形胶质细胞。简要总结反复暴露于简单的束缚应激会改变参与炎症的基因活性以及兴奋性神经递质谷氨酸的功能。小鼠脑海马体中的这些变化显示出差异，这些差异取决于小鼠品系和应激暴露的时长。应激对这些基因活性的影响可能导致行为改变。
