Down‐regulation of HTR1A‐modulated ACC activation contributes to stress‐induced visceral hyperalgesia in rats
| Autor: | Tingting Zhan, Lu Zhou, Liqian Xuan, Shuchang Xu, Lisha Yi, Haiqin Zhang, Ying Chen, Huihui Sun, Yuanxi Jiang |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine MAPK/ERK pathway Elevated plus maze medicine.medical_specialty Colon Physiology Down-Regulation Gyrus Cinguli Open field 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Western blot Internal medicine Animals Medicine Rats Wistar Receptor Protein kinase B Sensitization medicine.diagnostic_test Endocrine and Autonomic Systems business.industry Gastroenterology Rats 030104 developmental biology medicine.anatomical_structure Endocrinology Hyperalgesia Receptor Serotonin 5-HT1A business Stress Psychological 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Neurogastroenterology & Motility. 31 |
| ISSN: | 1365-2982 1350-1925 |
| DOI: | 10.1111/nmo.13620 |
| Popis: | Background Long-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. Methods The 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. Results The 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 & inferences Down-regulation of HTR1As modulates ACC activation probably through activating ERK and Akt pathways, thus contributes to the formation of stress-induced visceral hyperalgesia. |
| Databáze: | OpenAIRE |
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