Hare A S, Clarke G, Tolchard S
Department of Anatomy, University of Bristol, School of Medical Sciences, UK.
J Neuroendocrinol. 1995 Oct;7(10):791-9. doi: 10.1111/j.1365-2826.1995.tb00716.x.
In the present study the regions of the brain showing an increase in the number of FOS protein stained cells 180 min following intravenous saline or bacterial lipopolysaccharide (LPS) treatment were investigated and correlated with changes in body temperature and plasma corticosterone levels. Particular attention was given to the possible involvement of the circumventricular organs and regions of the brainstem containing central noradrenergic neurones. LPS at doses of 0.35, 3.5 and 50 micrograms caused highly significant increases in FOS protein expression in the organum vasculosum of lamina terminalis, the area postrema and the subfornical organ compared with saline controls. Marked increases in bacterial lipopolysaccharide-induced FOS protein expression were observed in the ventrolateral medulla, the nucleus of the solitary tract and the locus coeruleus which contain the A1, A2 and A6 noradrenergic neurones respectively. The changes in body temperature induced by LPS were found to be dependent upon the dose of LPS administered; the lowest dose employed (0.35 micrograms) induced an immediate and sustained fever, 3.5 micrograms LPS caused a biphasic response consisting of a hypothermic response followed by a febrile response, whereas 50 micrograms LPS induced a hypothermic response which then normalised by 160 min post-injection. Intravenous saline injection had no significant effect on body temperature. The occurance of LPS-induced hypothermia was coincident with increased FOS expression in the bed nucleus of stria terminalis, which houses vasopressinergic neurones involved in antipyresis, whereas in animals showing an LPS-induced febrile response there was no significant difference in the number of FOS stained cells in the bed nucleus of stria terminalis compared with saline treated animals. LPS also caused marked increases in FOS protein expression in the parvocellular regions of the paraventricular nucleus (pPVN) of the hypothalamus, the central nucleus of the amygdala and the ventral septal area. Plasma corticosterone was unaffected by the lowest dose of LPS (0.35 micrograms), however the higher doses employed (3.5 and 50 micrograms) caused significant increases in plasma corticosterone which correlated with the increases in the number of FOS stained cells in the pPVN. The results of the present study suggest that, in addition to the organum vasculosum of lamina terminalis, the area postrema and subfornical organ may be important in the responses to antigenic challenge that are mediated by the central nervous system. They also add support to the possible involvement of the bed nucleus of stria terminalis in LPS-induced hypothermia and of the involvement of the of the major noradrenergic cell groups (A1, A2 & A6) and a number of hypothalamic and extrahypothalamic forebrain regions in the interaction of immune and central nervous systems.
在本研究中，对静脉注射生理盐水或细菌脂多糖（LPS）180分钟后FOS蛋白染色细胞数量增加的脑区进行了研究，并将其与体温和血浆皮质酮水平的变化相关联。特别关注了室周器官和含有中枢去甲肾上腺素能神经元的脑干区域可能的参与情况。与生理盐水对照组相比，0.35、3.5和50微克剂量的LPS导致终板血管器、最后区和穹窿下器官中FOS蛋白表达显著增加。在分别含有A1、A2和A6去甲肾上腺素能神经元的腹外侧延髓、孤束核和蓝斑中观察到细菌脂多糖诱导的FOS蛋白表达显著增加。发现LPS诱导的体温变化取决于所给予的LPS剂量；使用的最低剂量（0.35微克）诱导立即且持续的发热，3.5微克LPS引起双相反应，包括低温反应后接着发热反应，而50微克LPS诱导低温反应，然后在注射后160分钟恢复正常。静脉注射生理盐水对体温无显著影响。LPS诱导的低温发生与终纹床核中FOS表达增加同时出现，终纹床核中含有参与解热的加压素能神经元，而在表现出LPS诱导发热反应的动物中，终纹床核中FOS染色细胞数量与生理盐水处理动物相比无显著差异。LPS还导致下丘脑室旁核小细胞区（pPVN）、杏仁中央核和腹侧隔区中FOS蛋白表达显著增加。最低剂量的LPS（0.35微克）对血浆皮质酮无影响，然而使用的较高剂量（3.5和50微克）导致血浆皮质酮显著增加，这与pPVN中FOS染色细胞数量的增加相关。本研究结果表明，除了终板血管器外，最后区和穹窿下器官在中枢神经系统介导的对抗抗原刺激的反应中可能很重要。它们还支持终纹床核可能参与LPS诱导的低温以及主要去甲肾上腺素能细胞群（A1、A2和A6）以及一些下丘脑和下丘脑外前脑区域参与免疫和中枢神经系统相互作用的可能性。
