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Brain mechanism and conditioning of emotional behavior induced by immunological stress

免疫应激诱发情绪行为的脑机制及调节

基本信息

批准号：
17590207
负责人：
KATAFUCHI Toshihiko
金额：
$ 2.3万
依托单位：
KYUSHU UNIVERCITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

项目摘要

Immunologically stress induced by infection, tumor, and autoimmunity activates not only immune system but also neural and endocrine systems, resulting in fever and ACTH secretion. At the same time disorders in higher brain functions such as emotional responses, impairment in learning and memory, and central fatigue, are also induced. The aim of the present study was to investigate brain mechanisms and conditioning of emotional behavior induced by immunological stress. The findings of the present study are as follows; (1) that intraperitoneal injection of poly I : C, a synthetic double stranded RNA, induced a decreased in running wheel activity in the home cage in rats, and produced a long-lasting increase in expression of interferon-a and serotonin transporter, which is known to be induced by interferon-a, in the cerebral cortex and hypothalamus, (2) that in vivo brain microdialysis revealed that the rat medial prefrontal cortex showed a long-lasting decrease in serotonin concentration probably due to the increased serotonin transporters, while noradrenaline concentration increased transiently and dopamine showed no changes, (3) that microinjection of interferon-a into the medial prefrontal cortex induced a decrease in serotonin levels, which was blocked by a selective serotonin reuptake inhibitor, fluoxetine, suggesting that the interferon-α-induced reduction of serotonin was due to the enhanced expression of serotonin transporter, (4) that the poly I:C-induced fatigue and anxiety were both attenuated by serotonin 1A receptor agonist, (5) that the poly I : C-induced fatigue was conditioned by drinking saccharin water, and this conditioning was extinguished by serotonin 1A receptor agonist, and (6) that these findings suggested that the poly I : C-induced infection stress model produced central fatigue and anxiety, in which brain interferon-and serotonin system were involved, and these responses could be conditioned.

感染、肿瘤和自身免疫引起的免疫应激不仅会激活免疫系统，还会激活神经和内分泌系统，导致发烧和ACTH分泌。同时还会诱发情绪反应、学习记忆障碍、中枢疲劳等大脑高级功能紊乱。本研究的目的是调查免疫应激引起的情绪行为的大脑机制和调节。本研究的结果如下： (1) 腹腔注射聚 I : C（一种合成的双链 RNA）可诱导大鼠笼内跑轮活动减少，并导致大脑皮层和下丘脑中干扰素-a 和血清素转运蛋白的表达持久增加，已知这是由干扰素-a 诱导的，(2) 体内脑微透析研究表明，大鼠内侧前额叶皮层的血清素浓度长期持续下降，可能是由于血清素转运蛋白增加，而去甲肾上腺素浓度短暂增加，而多巴胺没有变化；(3) 将干扰素-a显微注射到内侧前额叶皮层，引起血清素水平下降，而选择性血清素再摄取可阻止这种下降。抑制剂氟西汀，表明干扰素-α诱导的血清素减少是由于血清素转运蛋白表达增强所致，(4)多聚I:C诱导的疲劳和焦虑均被5-羟色胺1A受体激动剂减弱，(5)多聚I:C诱导的疲劳通过饮用糖精水得到调节，并且这种调节被 (6)这些发现表明，多聚I:C诱导的感染应激模型产生中枢疲劳和焦虑，其中涉及大脑干扰素和血清素系统，并且这些反应可以被调节。