Restraint stress differentially regulates inflammation and glutamate receptor gene expression in the hippocampus of C57BL/6 and BALB/c mice.

Restraint stress differentially regulates inflammation and glutamate receptor gene expression in the hippocampus of C57BL/6 and BALB/c mice.
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DOI:
10.1080/10253890.2017.1298587
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发表时间:
2017-03
期刊:
Stress (Amsterdam, Netherlands)
影响因子:
--
通讯作者:
Newton SS
Newton SS
中科院分区:
其他
文献类型:
--
作者:
Sathyanesan M;Haiar JM;Watt MJ;Newton SS

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近交系小鼠品系 C57BL/6 和 BALB/c 已广泛用于临床前精神病学研究。可用菌株的应激敏感性差异为测试药理学制剂和行为反应提供了有用的平台。先前的脑基因分析工作表明,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,包括一系列扩展的、多样化的和不可预测的压力源的复合压力范式会在海马体中诱导炎症相关基因。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,并通过采用简单的应激方案进行了测试,即重复暴露于相同的应激源 10 天,每天限制两个小时。我们使用定量 PCR 检查了雄性 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。升高的细胞因子基因包括肿瘤坏死因子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,我们还检查了两种菌株中束缚应激诱导的 12 个谷氨酸受体基因的调节。我们的结果表明,束缚应激足以提高 BABLB/c 和 C57BL/6 小鼠海马炎症相关基因的表达,但它们在诱导的基因和变化幅度方面有所不同。参与这种反应的细胞类型包括内皮细胞和星形胶质细胞。
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, two hours 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.
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