Down-regulation of HTR1A-modulated ACC activation contributes to stress-induced visceral hyperalgesia in rats
Down-regulation of HTR1A-modulated ACC activation contributes to stress-induced visceral hyperalgesia in rats
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HTR1A 调节的 ACC 激活的下调有助于大鼠应激诱导的内脏痛觉过敏。
DOI：
10.1111/nmo.13620
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Xu Shuchang
中科院分区：
文献类型：
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作者：
Yi Lisha;Sun Huihui;Zhang Haiqin;Chen Ying;Zhou Lu;Xuan Liqian;Zhan Tingting;Jiang Yuanxi;Xu Shuchang
长期应激被认为会引起内脏超敏反应并促进功能性胃肠疾病（fgid）。一些大脑区域如前扣带皮层（ACC）可能在产生内脏超敏反应中起重要作用；然而，其分子机制尚不清楚。本研究旨在探讨应激性内脏痛觉过敏大鼠中5 - HT1A受体（HTR1As）在激活ACC中的作用及其机制。方法采用慢性避水应激法（was）建立VH大鼠模型，采用肌电图法测定内脏敏感性。采用开阔场试验（OFT）和升高迷宫（EPM）对大鼠的焦虑样行为进行评价。为了过表达或下调HTR1A的表达，将表达绿色荧光蛋白的HTR1A特异性慢病毒注入ACC。Western blot观察蛋白表达水平。结果WAS组大鼠双侧ACC中HTR1A蛋白表达明显低于正常对照组（NC）和Sham - WAS组，而ACC中c - fos蛋白表达明显高于Sham - WAS组。下调HTR1As可诱导对照组大鼠的VH， ACC中c - fos、p - ERK和p - Akt的表达增加，而上调HTR1As可部分抑制ACC致敏和应激性内脏痛觉过敏。结论与推论HTR1As下调可能通过激活ERK和Akt通路来调节ACC的激活，从而促进应激性内脏痛觉过敏的形成。
BackgroundLong‐term stress was suggested to cause visceral hypersensitivity and promote functional gastrointestinal disorders (FGIDs). Some brain regions such as the anterior cingulate cortex (ACC) may play an important role for generating visceral hypersensitivity; however, its molecular mechanisms are not clear. This study aimed to explore the role of 5‐HT1A receptors (HTR1As) in activating ACC and corresponding mechanism, in stress‐induced visceral hyperalgesia rats.MethodsThe VH rat model was established by chronic water avoidance stress (WAS), and the visceral sensitivity was measured by electromyogram. Rat's anxiety‐like behaviors were evaluated by the open field test (OFT) and elevated plus maze (EPM). To overexpress or down‐regulate HTR1A expression, HTR1A‐specific lentivirus expressing the green fluorescent protein was administered into the ACC. Protein expression levels were observed by Western blot.ResultsThe protein expression of HTR1A in bilateral ACC in WAS group was significantly lower than that in normal control (NC) and Sham‐WAS groups, while the levels of c‐fos in the ACC of WAS rats were significantly higher. Down‐regulation of HTR1As could induce VH in control rats with the increased expression of c‐fos, p‐ERK, and p‐Akt in ACC, while up‐regulation of HTR1As in the ACC could partly inhibit ACC sensitization and stress‐induced visceral hyperalgesia.Conclusions & InferencesDown‐regulation of HTR1As modulates ACC activation probably through activating ERK and Akt pathways, thus contributes to the formation of stress‐induced visceral hyperalgesia.