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Analysis of adaptation mechanisms during environmental stress through the neural-immune interaction.

通过神经-免疫相互作用分析环境应激期间的适应机制。

基本信息

批准号：
12470011
负责人：
KATAFUCHI Toshihiko
金额：
$ 9.09万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

(1) Amount of c-fos mRNA increased in the medial preoptic area (MPO), lateral hypothalamic area (LHA), and ventromedial hypothalamus (VMH) during cold exposure (4 ℃, 1 hr), while CRF mRNA increased in the MPO and paraventricular hypothalamus (PVN) during heat exposure (33 ℃, 1 hr) and in the MPO and LHA during cold. (2) Intraperitoneal injection of poly I:C (mg/kg) in rats induced suppression of spontaneous running wheel activity for more than one week. During this period IFN-α and serotonin transporter (5-HTT) mRNA increased in the cortex and hypothalamus. (3) Heat exposure induced increase in IL-1β, COX-2 and inhibitor of nuclear factor (NF)-κB-β mRNAs, as well as lipopolysaccharide (LPS) content in the cortex of aged rats. Since pretreatment with an endotoxin inhibitor attenuated the increases in these mRNAs and LPS levels, it was suggested that bacterial translocation induced by heat exposure was one of the mechanisms of the increased expression of IL-1β and its related substances mRNAs in the brain. (4) In vivo brain microdialysis revealed that the extracellular concentration of 5-HT in the prefrontal cortex decreased after poly I:C injection. In addition, the poly I:C-induced suppression of the running wheel activity was attenuated by 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetraline (8-OH-DPAT). (5) Application of a hematopoietic cytokine, stem cell factor (SCF), modulated paired-pulse facilitation in the mossy fiber-CA3 pathway in the mouse hippocampal slices, suggesting that SCF plays a role in the synaptic plasticity in the hippocampus.

(1)冷暴露（4 ℃，1 h）时，下丘脑腹内侧区（VMH）、视前内侧区（MPO）、下丘脑外侧区（LHA）c-fos mRNA表达增加;热暴露（33 ℃，1 h）时，下丘脑腹内侧区（VMH）、视前内侧区（MPO）、室旁核（PVN）CRFmRNA表达增加; (2)腹腔注射Poly I：C（mg/kg）可使大鼠自发性转轮活动抑制一周以上。在此期间，皮质和下丘脑中的IFN-α和5-羟色胺转运蛋白（5-HTT）mRNA增加。(3)热暴露可诱导老龄大鼠大脑皮质IL-1β、考克斯-2和核因子（NF）-κB-β抑制因子的mRNA表达及脂多糖（LPS）含量增加。由于内毒素抑制剂预处理减弱了这些mRNA和LPS水平的增加，因此提示热暴露诱导的细菌移位是脑中IL-1β及其相关物质mRNA表达增加的机制之一。(4)在体脑微透析显示，前额叶皮质细胞外5-HT浓度下降后，聚I：C注射。5-HT_（1A）受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）可明显抑制poly I：C对小鼠转轮活动的抑制作用。(5)应用造血细胞因子干细胞因子（SCF）对小鼠海马脑片苔藓纤维-CA 3通路的成对脉冲易化进行了调节，提示SCF在海马突触可塑性中发挥作用。