Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation
Genesis of anxiety, depression, and ongoing abdominal discomfort in ulcerative colitis-like colon inflammation
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DOI：
10.1152/ajpregu.00298.2014
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Sarna, Sushil K.
中科院分区：
文献类型：
--
作者：
Chen, Jinghong;Winston, John H.;Sarna, Sushil K.
心理障碍在炎症性肠病患者中普遍存在；其潜在机制尚不清楚。我们验证了这样的假设：葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎样炎症加剧了结肠投射传入神经元持续的自发活动，导致大鼠腹部不适、焦虑和抑郁样行为。在本研究中，我们使用条件位置偏好和标准测试焦虑和抑郁样行为。DSS大鼠在炎症开始后10至20天出现焦虑和抑郁样行为。单纤维记录显示L6-S1背根神经节（DRG）根的自发活动频率增加。树脂干扰素（RTX）对表达瞬时受体电位香草样蛋白1 （TRPV1）的结肠传入神经的长期脱敏抑制了自发活性，以及焦虑和抑郁样行为。在DSS大鼠中，结肠内给药利多卡因对结肠事件自发活动的降低产生了强大的条件位置偏好（CPP），而在对照组大鼠中则没有。膜片钳研究表明，DSS大鼠在电流注射后，结肠突出的L6-S1 DRG神经元的静息膜电位显著降低，流变酶降低，对产生动作电位序列的敏感化。DSS炎症上调瞬时受体电位锚蛋白1和TRPV1通道mRNA水平，下调K(v)1.1和K(v)1.4通道mRNA水平。溃疡性结肠炎样炎症在大鼠中引起焦虑和抑郁样行为，以及持续的腹部不适，通过加剧结肠投射传入神经元的自发活动。电压和配体门控通道表达的改变与结肠炎症后情绪障碍的诱导有关。
Psychological disorders are prevalent in patients with inflammatory bowel disease; the underlying mechanisms remain unknown. We tested the hypothesis that ulcerative colitis-like inflammation induced by dextran sodium sulfate (DSS) exacerbates the ongoing spontaneous activity in colon-projecting afferent neurons that induces abdominal discomfort and anxiety, and depressive-like behaviors in rats. In this study, we used the conditioned place preference and standard tests for anxiety-and depression-like behaviors. DSS rats developed anxiety-and depression-like behaviors 10 to 20 days after the start of inflammation. Single-fiber recordings showed an increase in the frequency of spontaneous activity in L6-S1 dorsal root ganglion (DRG) roots. Prolonged desensitization of transient receptor potential vanilloid 1 (TRPV1)-expressing colonic afferents by resiniferatoxin (RTX) suppressed the spontaneous activity, as well as the anxiety-and depressive-like behaviors. Reduction in spontaneous activity in colon afferents by intracolonic administration of lidocaine produced robust conditioned place preference (CPP) in DSS rats, but not in control rats. Patch-clamp studies demonstrated a significant decrease in the resting membrane potential, lower rheobase, and sensitization of colon-projecting L6-S1 DRG neurons to generate trains of action potentials in response to current injection in DSS rats. DSS inflammation upregulated the mRNA levels of transient receptor potential ankyrin 1 and TRPV1 channels and downregulated that of K(v)1.1 and K(v)1.4 channels. Ulcerative colitis-like inflammation in rats induces anxiety-and depression-like behaviors, as well as ongoing abdominal discomfort by exacerbating the spontaneous activity in the colon-projecting afferent neurons. Alterations in the expression of voltage-and ligand-gated channels are associated with the induction of mood disorders following colon inflammation.