TNF activates astrocytes and catecholaminergic neurons in the solitary nucleus: implications for autonomic control.

TNF activates astrocytes and catecholaminergic neurons in the solitary nucleus: implications for autonomic control.
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DOI:
10.1016/j.brainres.2009.03.059
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发表时间:
2009-06-01
期刊:
影响因子:
2.9
通讯作者:
Rogers RC
Rogers RC
中科院分区:
医学3区
文献类型:
--
作者:
Hermann GE;Rogers RC

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肿瘤坏死因子[TNF]产生与胃肠道停滞相关的严重厌食症。我们的工作表明,TNF的主要作用部位是通过孤束核内的迷走神经传入引起胃功能的变化。这些传入神经的兴奋可能通过激活下游NST神经元而引起胃停滞,下游NST神经元继而通过对投射到胃的迷走神经背侧运动核中的神经元的作用而抑制胃运动。我们对胃迷走-迷走反射的平行研究结果表明,NST中的去甲肾上腺素能神经元对反射性胃抑制的产生特别重要。这些观察结果的收敛使我们假设,在NST的TNF行动可能会优先影响假定的去甲肾上腺素能神经元。目前的研究证实了我们在NST中观察到的细胞的剂量依赖性TNF活化[如cFOS产生所示]。NST中这些TNF激活的神经元的表型同一性为~29%酪氨酸羟化酶[TH]阳性[即,推测为去甲肾上腺素能神经元]。相反,TNF暴露后,不到10%的氮能神经元被激活。令人惊讶的是,NST中另外54%的cFOS活化细胞被表型鉴定为星形胶质细胞。与以前的观察一起,目前的结果表明,强烈或长期的迷走神经传入活动[由内脏通路活动,肠道激素或细胞因子如TNF的作用引起]可以改变局部星形胶质细胞立即早期基因表达,这反过来又可以引起迷走神经反射回路敏感性的长期,也许是永久性的变化。
Tumor necrosis factor [TNF] produces a profound anorexia associated with gastrointestinal stasis. Our work suggests that the principal site of action of TNF to cause this change in gastric function is via vagal afferents within the nucleus of the solitary tract [NST]. Excitation of these afferents presumably causes gastric stasis by activating downstream NST neurons that, in turn, suppress gastric motility via action on neurons in the dorsal motor nucleus of the vagus that project to the stomach. Results from our parallel studies on gastric vago-vagal reflexes suggest that noradrenergic neurons in the NST are particularly important to the generation of reflex gastroinhibition. Convergence of these observations led us to hypothesize that TNF action in the NST may preferentially affect putative noradrenergic neurons. The current study confirms our observations of a dose-dependent TNF activation of cells [as indicated by cFOS production] in the NST. The phenotypic identity of these TNF-activated neurons in the NST was ~29% tyrosine-hydroxylase [TH]-positive [i.e., presumably noradrenergic neurons]. In contrast, less than 10% of the nitrergic neurons were activated after TNF exposure. Surprisingly, another 54% of the cFOS activated cells in the NST were phenotypically identified to be astrocytes. Taken together with previous observations, the present results suggest that intense or prolonged vagal afferent activity [induced by visceral pathway activity, action of gut hormones or cytokines such as TNF] can alter local astrocyte immediate early gene expression that, in turn, can provoke long-term, perhaps permanent changes in the sensitivity of vagal-reflex circuitry.
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