From Gut to Brain: Alteration in Inflammation Markers in the Brain of Dextran Sodium Sulfate-induced Colitis Model Mice.
From Gut to Brain: Alteration in Inflammation Markers in the Brain of Dextran Sodium Sulfate-induced Colitis Model Mice.
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DOI：
10.9758/cpn.2018.16.4.422
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发表时间：
2018-11-30
期刊：
影响因子：
--
通讯作者：
Woo J
中科院分区：
文献类型：
--
作者：
Do J;Woo J
抑郁症和认知功能障碍等神经精神症状通常发生在炎症性肠病（IBD）中。在脑肠轴模型的背景下，结肠炎可以以自下而上的方式导致大脑功能的改变。在这里，研究了结肠炎中下丘脑-垂体-肾上腺轴反应的变化以及大脑中炎症相关标记物。葡聚糖硫酸钠（DSS）用于建立小鼠结肠炎模型。用DSS处理小鼠3或7天并处死。我们分析了海马、下丘脑和杏仁核中脑源性神经营养因子 (BDNF)、环加氧酶 2 (COX-2) 和胶质纤维酸性蛋白 (GFAP) 的基因表达以及 GFAP 的表达。此外，还测量了 C 反应蛋白 (CRP) 和血清皮质醇/皮质酮的水平。炎症相关标记物的变化根据大脑区域和暴露时间而变化。在海马体中，暴露于 DSS 期间，COX-2 mRNA、GFAP mRNA 和 GFAP 表达上调。然而，在下丘脑中，COX-2 mRNA 在治疗后仅 3 天就上调。在杏仁核中，BDNF 和 COX-2 mRNA 下调。 DSS 治疗第 7 天时，CRP 和皮质酮表达增加。IBD 可能以自下而上的方式导致神经炎症，并且这种效应根据大脑区域的不同而不同。从 DSS 治疗的第三天开始，与压力相关的激素和血清炎症标志物（例如 CRP）上调。因此，需要早期积极干预来预防IBD引起的心理和行为变化，而针对特定区域的研究有助于了解IBD影响大脑的精确机制。
Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclo-oxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.
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