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

细菌内毒素引起的外周炎症诱导脑内细胞因子的表达，引起厌食和发热反应。直接电刺激迷走神经传入神经本身可诱导脑内IL-1β的产生，激活下丘脑-垂体-肾上腺轴。因此，在感染和炎症的急性期，迷走神经传入可能在向大脑传递外周信号方面发挥重要作用。越来越多的证据表明，ob基因的产物瘦素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、海马体、皮质、小脑和脑干中IL-1β的转录。Leptin可增加原代培养的小鼠神经胶质细胞IL-1β基因的表达，提示Leptin诱导的IL-1β转录本的靶细胞可能是胶质细胞。瘦素应用于缺乏功能性Ob-Rb受体的db/db小鼠，增加了下丘脑IL-1β基因水平，与e-…类似与正常小鼠相比有更多的实验。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神经传入神经而起调节作用。由于迷走神经切断不能调节瘦素诱导的IL-1β在脑内的表达，提示循环中的瘦素直接作用于脑内，并通过瘦素受体的短亚型诱导IL-1β转录。SAMP8菌株显示出与年龄相关的学习和记忆退化。10月龄SAMP8大鼠脑组织中，IL-1β在海马区和下丘脑的表达明显增强，大脑皮层和海马区的肿瘤坏死因子-α和IL-6的表达明显增强。促炎症细胞因子在脑内的表达增加可能与SAMPS的年龄相关性神经元功能障碍和/或学习障碍有关。较少

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