Marques Fernanda, Sousa João C, Coppola Giovanni, Geschwind Daniel H, Sousa Nuno, Palha Joana A, Correia-Neves Margarida
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal.
BMC Neurosci. 2009 Nov 18;10:135. doi: 10.1186/1471-2202-10-135.
Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid.
In the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection.
These observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated.
慢性全身性炎症会引发中枢神经系统的改变,这可能与神经退行性疾病(如多发性硬化症和阿尔茨海默病)中报道的潜在炎症成分有关。然而,外周炎症是否以及如何在这些疾病中促成脑部炎症反应,目前还远未明确。作为将血液与大脑分隔开的屏障的一部分,脉络丛主要通过脑脊液成分的改变,将炎症免疫信号传递到大脑中。
在本研究中,我们使用微阵列分析方法,研究了小鼠脉络丛的基因表达谱,以响应每两周腹腔注射一次脂多糖,持续三个月所诱导的反复炎症刺激;在最后一次注射脂多糖后的第3天和第15天处死小鼠。数据显示,脉络丛通过改变多个基因的表达谱,对反复的炎症刺激表现出持续的反应。在总共24,000个探针中,最后一次注射脂多糖后3天,有369个上调,167个下调,而在15天时,这一数量分别降至98个和128个。显示出最显著变化的通路包括那些促进细胞进入脑脊液的通路,以及那些参与对感染的固有免疫反应的通路。
这些观察结果有助于更好地理解大脑对外周炎症的反应,并为研究它们对已知涉及炎症的几种中枢神经系统疾病进展的影响铺平了道路。