Szot Patricia, Franklin Allyn, Figlewicz Dianne P, Beuca Timothy Petru, Bullock Kristin, Hansen Kim, Banks William A, Raskind Murray A, Peskind Elaine R
Mental Illness Research, Education and Clinical Center, Seattle, WA, USA.
Mental Illness Research, Education and Clinical Center, Seattle, WA, USA.
Neuroscience. 2017 Jul 4;355:9-21. doi: 10.1016/j.neuroscience.2017.04.028. Epub 2017 Apr 27.
Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer's disease, Parkinson's disease, and traumatic brain injury. However, exactly how neuroinflammation leads to, or contributes to, these central disorders is unclear. The objective of the study was to examine and compare the expression of mRNAs for interleukin-6 (IL-6), IL-7, IL-10 and the receptors for IL-6 (IL-6R) and IL-7 (IL-7R) using in situ hybridization in discrete brain regions and in the spleen after multiple injections of 3mg/kg lipopolysaccharide (LPS), a model of neuroinflammation. In the spleen, LPS significantly elevated IL-6 mRNA expression, then IL-10 mRNA, with no effect on IL-7 or IL-7R mRNA, while significantly decreasing IL-6R mRNA expression. In the CNS, LPS administration had the greatest effect on IL-6 and IL-6R mRNA. LPS increased IL-6 mRNA expression only in non-neuronal cells throughout the brain, but significantly elevated IL-6R mRNA in neuronal populations, where observed, except the cerebellum. LPS resulted in variable effects on IL-10 mRNA, and had no effect on IL-7 or IL-7R mRNA expression. These studies indicate that LPS-induced neuroinflammation has substantial but variable effects on the regional and cellular patterns of CNS IL-6, IL-7 and IL-10, and for IL-6R and IL-7R mRNA expression. It is apparent that administration of LPS can affect non-neuronal and neuronal cells in the brain. Further research is required to determine how CNS inflammatory changes associated with IL-6, IL-10 and IL-6R could in turn contribute to the development of CNS neurological disorders.
神经炎症被认为是包括抑郁症、阿尔茨海默病、帕金森病和创伤性脑损伤在内的几种中枢神经系统（CNS）疾病发展过程中的一个重要组成部分。然而，神经炎症究竟如何导致或促成这些中枢性疾病尚不清楚。本研究的目的是在多次注射3mg/kg脂多糖（LPS）（一种神经炎症模型）后，使用原位杂交技术检测并比较离散脑区和脾脏中白细胞介素-6（IL-6）、IL-7、IL-10以及IL-6受体（IL-6R）和IL-7受体（IL-7R）的mRNA表达。在脾脏中，LPS显著提高了IL-6 mRNA的表达，然后是IL-10 mRNA，对IL-7或IL-7R mRNA没有影响，同时显著降低了IL-6R mRNA的表达。在中枢神经系统中，LPS给药对IL-6和IL-6R mRNA的影响最大。LPS仅在全脑的非神经元细胞中增加IL-6 mRNA的表达，但在观察到的神经元群体中显著提高IL-6R mRNA的表达，小脑除外。LPS对IL-10 mRNA产生了不同的影响，对IL-7或IL-7R mRNA的表达没有影响。这些研究表明，LPS诱导的神经炎症对中枢神经系统IL-6、IL-7和IL-10以及IL-6R和IL-7R mRNA表达的区域和细胞模式有显著但不同的影响。显然，LPS给药可影响大脑中的非神经元和神经元细胞。需要进一步研究以确定与IL-6、IL-10和IL-6R相关的中枢神经系统炎症变化如何反过来促成中枢神经系统神经疾病的发展。
