Abstract:
Ulcerative colitis (UC) is a common inflammatory bowel disease with a complex origin in clinical settings. It is frequently accompanied by negative emotional responses, including anxiety and depression. Enteric glial cells (EGCs) are important components of the gut-brain axis and are involved in the development of the enteric nervous system (ENS), intestinal neuroimmune, and regulation of intestinal motor functions. Since there is limited research encompassing the regulatory function of EGCs in anxiety- and depression-like behaviors induced by UC, this study aims to reveal their regulatory role in such behaviors and associated intestinal inflammation. This study applied morphological, molecular biological, and behavioral methods to observe the morphological and functional changes of EGCs in UC mice. The results indicated a significant activation of EGCs in the ENS of dextran sodium sulfate -induced UC mice. This activation was evidenced by morphological alterations, such as elongation or terminal swelling of processes. Besides EGCs activation, UC mice exhibited significantly elevated expression levels of pro-inflammatory cytokines in the peripheral blood, accompanied by anxiety- and depression-like behaviors. The inhibition of EGCs activity within the ENS can ameliorate the anxiety- and depression-like behaviors caused by UC. Our data suggest that UC and its resulting behaviors may be related to the activation of EGCs within the ENS. Moreover, the modulation of intestinal inflammation through inhibition of EGCs activation emerges as a promising clinical approach for alleviating UC-induced anxiety- and depression-like behaviors.
摘要:
溃疡性结肠炎(UC)是一种常见的炎症性肠病,在临床上起源复杂。它经常伴随着负面的情绪反应,包括焦虑和抑郁.肠神经胶质细胞(EGCs)是肠-脑轴的重要组成部分,参与肠神经系统(ENS)的发育,肠道神经免疫,和调节肠道运动功能。由于对UC诱导的焦虑和抑郁样行为中EGCs的调节功能的研究有限,本研究旨在揭示它们在此类行为和相关肠道炎症中的调节作用。本研究应用形态学,分子生物学,和行为学方法观察UC小鼠EGCs的形态和功能变化。结果表明在葡聚糖硫酸钠诱导的UC小鼠的ENS中EGCs显著活化。这种激活由形态学改变证明,如过程的伸长或最终膨胀。除了EGCs激活,UC小鼠外周血促炎细胞因子表达水平显著升高,伴随着焦虑和抑郁的行为。在ENS内抑制EGCs活性可以改善由UC引起的焦虑和抑郁样行为。我们的数据表明,UC及其产生的行为可能与ENS内EGC的激活有关。此外,通过抑制EGCs激活来调节肠道炎症是缓解UC诱导的焦虑和抑郁样行为的有希望的临床方法。