权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The study of brain cytokine expression mediated by the vagus nerve, leptin and aging

迷走神经、瘦素介导的脑细胞因子表达与衰老的研究

基本信息

批准号：
12672103
负责人：
OKUMA Yasunobu
金额：
$ 2.18万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672103/
关键词：
afferent vagus nerve interlcukin-1β infection and inflammation leptin glial cells Senescence-accelerated mouse (SAM)learning and memory Aging

项目摘要

Peripheral inflammation induced by bacterial endotoxin induces cytokine expression in the brain, anorexial and fever responses. Direct electrical stimulation of the afferent vagus nerves itself can induce production of IL-1β in brain and activate the HPA axis. Therefore, the afferent vagus nerve may play an important role in transmitting peripheral signals to the brain in the acute phase of infection and inflammation. Increasing evidence has suggested that leptin, the product of the ob gene may interact with cytokines in immune system. Peripherally applied leptin increased IL-1β transcripts in the hypothalamus, the hippocampus, the cortex, the cerebellum and the brainstem. Leptin increased the expression of IL-1β mRNA in mouse primary cultured glial cells, indicating that tone of the target cells of the leptin-induced IL-1β transcript may be a gial cells. Leptin applied to the db/db mice, which lack functional Ob-Rb receptor, increased IL-1β mRNA levels in the hypothalamus to similar e … More xtents as normal mice. These results indicate that the leptin-induced cytokine expression in the brain probably be mediated through short isoform of leptin receptor. We examined whether leptin -induced IL-1β induction is mediating through activating vagal afferent nerve activity. Since vagotomy did not modulate leptin-inducede IL-1β expression in the brain, it is suggested that circulating leptin directly acts in the brain and induces IL-1β transcript via short isoform of leptin receptor.The senescence-accelerated mouse (SAM) is known to be a marine mode, for accelerated aging. The SAMP8 strain shows age-related deterioration of learning and memory. In the brain of 10 months old SAMP8, the expression of IL-1β in the hippocampus and hypothalamus, and in TNF-α and IL-6 in the cerebral cortex and the hippocampus were significantly elevated. Increases in expression of proinflammatory cytokines in the brain may be involved in the age-related neurl dysfunction and/or learning deficiency in SAMPS. Less

由细菌内毒素诱导的外周炎症诱导脑中细胞因子的表达、轴向和发热反应。直接电刺激迷走传入神经本身可诱导脑内IL-1β的产生并激活HPA轴。因此，迷走传入神经可能在感染和炎症急性期将外周信号传递到大脑中起重要作用。越来越多的证据表明瘦素是ob基因的产物，它可能与免疫系统中的细胞因子相互作用。外周应用瘦素可增加下丘脑、海马、皮质、小脑和脑干中IL-1β的转录。Leptin可增加原代培养的小鼠胶质细胞IL-1β mRNA的表达，提示Leptin诱导IL-1β转录的靶细胞可能是胶质细胞。将瘦素应用于缺乏功能性Ob-Rb受体的db/db小鼠，可使下丘脑中IL-1β mRNA水平增加至与正常小鼠相似的水平。 ...更多信息与正常小鼠一样。这些结果表明瘦素诱导的细胞因子在脑内的表达可能是通过瘦素受体的短亚型介导的。我们研究了瘦素诱导的IL-1β诱导是否通过激活迷走传入神经活动介导。由于迷走神经切断不调节瘦素诱导的脑内IL-1β的表达，提示循环中的瘦素直接作用于脑内，通过瘦素受体的短亚型诱导IL-1β的转录。SAMP 8菌株显示出与年龄相关的学习和记忆衰退。10月龄SAMP 8脑中，海马和下丘脑中IL-1β的表达以及大脑皮质和海马中TNF-α和IL-6的表达均明显升高。脑内促炎细胞因子表达增加可能参与SAMPS中与年龄相关的神经功能障碍和/或学习缺陷。少