DISTRIBUTION AND CHARACTERIZATION OF TUMOR NECROSIS FACTOR-ALPHA-LIKE IMMUNOREACTIVITY IN THE MURINE CENTRAL-NERVOUS-SYSTEM
DISTRIBUTION AND CHARACTERIZATION OF TUMOR NECROSIS FACTOR-ALPHA-LIKE IMMUNOREACTIVITY IN THE MURINE CENTRAL-NERVOUS-SYSTEM
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DOI：
10.1002/cne.903370403
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发表时间：
1993-11-22
影响因子：
2.5
通讯作者：
SAPER, CB
中科院分区：
文献类型：
--
作者：
BREDER, CD;TSUJIMOTO, M;SAPER, CB
肿瘤坏死因子-α（TNF α）是在感染和炎症期间从巨噬细胞释放的蛋白质。最近的研究表明，它在中枢神经系统内有几种作用，包括发热，增强慢波睡眠和刺激垂体激素分泌。我们已经提出，TNF α可能是由中枢神经系统中的神经元合成的，并在参与这些活动的中枢控制的通路中用作神经调质。为了验证这一假设，我们使用了抗重组鼠（rm）TNF α的抗血清，采用间接免疫过氧化物酶技术对鼠CNS进行化学染色。小鼠脑匀浆的Western印迹分析显示一条电泳迁移率与rmTNF α相同的条带。我们确定TNFa样免疫反应（IR）神经元在下丘脑，在床核的终纹，中缝尾侧核，和沿着腹侧脑桥和延髓表面。三叉神经支配广泛分布于中枢神经系统，尤其是涉及自主神经和内分泌调节的区域，包括下丘脑、杏仁核、终纹床核、臂旁核、迷走神经背侧复合体、疑核和胸交感节前细胞柱。我们的数据表明，TNF α可能作为一种神经调节剂，在中枢通路参与调节的自主神经，内分泌和行为成分的急性期炎症和感染的反应。(C)1993 Wiley-Liss，Inc.
Tumor necrosis factor-alpha (TNFalpha) is a protein released from macrophages during infection and inflammation. Recent studies suggest that it has several effects within the central nervous system, including generation of fever, enhancement of slow wave sleep, and stimulation of pituitary hormone secretion. We have proposed that TNFalpha may be synthesized by neurons in the CNS and used as a neuromodulator in the pathways involved in the central control of these activities. To test this hypothesis, we have used an antiserum raised against recombinant murine (rm) TNFalpha with an indirect immunoperoxidase technique to stain the murine CNS immunohistochemically. Western blot analysis of mouse brain homogenates revealed one band with electrophoretic mobility identical to that of rmTNFalpha. We identified TNFalpha-like immunoreactive (ir) neurons in the hypothalamus, in the bed nucleus of the stria terminalis, in the caudal raphe nuclei, and along the ventral pontine and medullary surface. TNFalphair innervation was widespread within the CNS, particularly in areas involved in autonomic and endocrine regulation, including the hypothalamus, amygdala, bed nucleus of the stria terminalis, parabrachial nucleus, dorsal vagal complex, nucleus ambiguus, and thoracic sympathetic preganglionic cell column. Our data suggest that TNFalpha may serve as a neuromodulator in central pathways involved in the regulation of the autonomic, endocrine and behavioral components of the acute-phase response to inflammation and infection. (C) 1993 Wiley-Liss, Inc.