Breder C D, Tsujimoto M, Terano Y, Scott D W, Saper C B
Department of Pharmacology, University of Chicago, Illinois 60637.
J Comp Neurol. 1993 Nov 22;337(4):543-67. doi: 10.1002/cne.903370403.
Tumor necrosis factor-alpha (TNF alpha) 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 TNF alpha 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) TNF alpha 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 rmTNF alpha. We identified TNF alpha-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. TNF alpha ir 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 TNF alpha 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.
肿瘤坏死因子-α（TNFα）是巨噬细胞在感染和炎症期间释放的一种蛋白质。最近的研究表明，它在中枢神经系统内具有多种作用，包括引起发热、增强慢波睡眠以及刺激垂体激素分泌。我们提出TNFα可能由中枢神经系统中的神经元合成，并在参与这些活动中枢控制的通路中用作神经调节剂。为了验证这一假设，我们使用了针对重组鼠（rm）TNFα产生的抗血清，采用间接免疫过氧化物酶技术对鼠中枢神经系统进行免疫组织化学染色。对小鼠脑匀浆的蛋白质免疫印迹分析显示，有一条带的电泳迁移率与rmTNFα相同。我们在下丘脑、终纹床核、尾侧中缝核以及沿脑桥腹侧和延髓表面鉴定出了TNFα样免疫反应性（ir）神经元。TNFα ir神经支配在中枢神经系统内广泛分布，尤其是在参与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、迷走背核复合体、疑核以及胸段交感神经节前细胞柱。我们的数据表明，TNFα可能在参与调节对炎症和感染急性期反应的自主神经、内分泌和行为成分的中枢通路中充当神经调节剂。
