Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Neuroscience. 2017 Dec 16;366:124-137. doi: 10.1016/j.neuroscience.2017.10.023. Epub 2017 Oct 26.
Depression and anxiety are common comorbid disorders observed in patients with inflammatory bowel disease (IBD). Increasing line of evidence indicates that immune-inflammatory responses are involved in co-occurrence of mood disorders and IBD. However, the mechanisms through which immune-inflammatory pathways modulate this comorbidity are not yet understood. This study investigated the role of innate immunity in the development of behavioral abnormalities associated with an animal model of Crohn's disease (CD). To do this, we induced colitis in male adult mice by intrarectal (i.r.) injection of DNBS (Dinitrobenzene sulfonic acid). After 3 days, we performed behavioral tests for anxiety- and depressive-like behaviors as well as tissue collection. Our results showed that DNBS-induced colonic inflammatory responses were accompanied by infiltration of inflammatory cells, and increased expression of genes involved in toll-like receptor signaling pathway in intestinal tissue. Furthermore, the DNBS-treated mice showed depressive- and anxiety-like behaviors which were associated with increased expression of the inflammatory genes and abnormal mitochondrial function in the hippocampus. These results suggest that peripheral inflammation is able to increase the transcriptional level of the genes in toll-like receptor pathway, induces abnormal mitochondrial function in the hippocampus, and these negative effects may be involved in the co-occurrence of anxiety and depression in early stages of CD.
抑郁和焦虑是炎症性肠病（IBD）患者常见的共病。越来越多的证据表明，免疫炎症反应与心境障碍和 IBD 的共病有关。然而，免疫炎症途径通过何种机制调节这种共病尚不清楚。本研究探讨了固有免疫在与克罗恩病（CD）动物模型相关的行为异常发展中的作用。为此，我们通过直肠内（i.r.）注射二硝基苯磺酸（DNBS）诱导成年雄性小鼠结肠炎。3 天后，我们进行了焦虑和抑郁样行为以及组织收集的行为测试。我们的结果表明，DNBS 诱导的结肠炎症反应伴随着炎症细胞的浸润，以及肠道组织中参与 Toll 样受体信号通路的基因表达增加。此外，DNBS 处理的小鼠表现出抑郁和焦虑样行为，这与海马中炎症基因表达增加和线粒体功能异常有关。这些结果表明，外周炎症能够增加 Toll 样受体通路中基因的转录水平，诱导海马中线粒体功能异常，这些负面影响可能与 CD 早期焦虑和抑郁的共病有关。
