Bette Michael, Kaut Oliver, Schäfer Martin K-H, Weihe Eberhard
Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps-University Marburg, Robert-Koch-Strasse 8, 35033 Marburg, Germany.
J Comp Neurol. 2003 Oct 20;465(3):417-30. doi: 10.1002/cne.10877.
Serum tumor necrosis factor (TNF) functions as a mediator of the immune-to-brain axis. Numerous TNF receptor-mediated effects on the nervous system are described but the knowledge about the regional and cellular expression of TNF receptor p55TNFR and p75TNFR in vivo is far from being complete. It is unclear whether TNF mediates its neuroimmune effects alone or in combination with other factors, e.g., bacterial mitogens. Here, we investigated the distribution of TNFalpha, p55TNFR, and p75TNFR in normal mouse brain and examined the stimulus-specific effects of lipopolysaccharide (LPS) and staphylococcal enterotoxin B (SEB) on the expression of the cerebral TNF system. Both mitogens caused enhanced TNFalpha serum levels and induced c-fos mRNA in the paraventricular nucleus but exhibited different effects on the cerebral gene expression of the TNF system. LPS but not SEB rapidly induced TNFalpha mRNA in circumventricular organs (CVOs) followed by spreading of TNFalpha mRNA into brain parenchyma close to the CVOs. The p55TNFR gene was constitutively expressed in many neurons with high levels in brainstem motor nuclei and in neurons of the sensory mesencephalic trigeminal nucleus. Moderate levels of p75TNFR mRNA were seen in single cells scattered throughout the brain in a pattern resembling microglia. Neither LPS nor SEB modulated the p55TNFR gene expression in any region or cell type of the brain, and LPS but not SEB induced p75TNFR mRNA in the CVOs. Thus, enhanced TNF serum levels able to stimulate c-fos mRNA expression in the paraventricular nucleus did not necessarily result in a modulation of the cerebral TNF system.
血清肿瘤坏死因子（TNF）作为免疫-脑轴的介质发挥作用。关于TNF受体对神经系统的众多介导作用已有描述，但关于TNF受体p55TNFR和p75TNFR在体内的区域和细胞表达的知识仍远未完善。尚不清楚TNF是单独介导其神经免疫作用，还是与其他因素（如细菌促细胞分裂剂）共同介导。在此，我们研究了正常小鼠脑中TNFα、p55TNFR和p75TNFR的分布，并检测了脂多糖（LPS）和葡萄球菌肠毒素B（SEB）对脑TNF系统表达的刺激特异性作用。两种促细胞分裂剂均导致血清TNFα水平升高，并诱导室旁核中的c-fos mRNA，但对脑TNF系统的基因表达表现出不同影响。LPS而非SEB能迅速诱导室周器官（CVO）中的TNFα mRNA，随后TNFα mRNA扩散至靠近CVO的脑实质。p55TNFR基因在许多神经元中组成性表达，在脑干运动核和感觉中脑三叉神经核的神经元中表达水平较高。在整个脑中散在分布的单个细胞中可见中等水平的p75TNFR mRNA，其分布模式类似于小胶质细胞。LPS和SEB均未调节脑中任何区域或细胞类型的p55TNFR基因表达，且LPS而非SEB能诱导CVO中的p75TNFR mRNA。因此，能够刺激室旁核中c-fos mRNA表达的升高的TNF血清水平不一定会导致脑TNF系统的调节。
