The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats

Previous studies have shown that acute stress-induced gastric mucosal damage is linked to excessive activation of parasympathetic nervous system. The Insular Cortex (IC), the higher centers of the parasympathetic nervous system, serves as both the integration site of gastric sensory information and...

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Main Authors: Zepeng Wang, Xinyu Li, Yuanyuan Li, Xuehan Sun, Yuxue Wang, Tong Lu, Dongqin Zhao, Xiaoli Ma, Haiji Sun
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Neurobiology of Stress
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352289525000177
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author Zepeng Wang
Xinyu Li
Yuanyuan Li
Xuehan Sun
Yuxue Wang
Tong Lu
Dongqin Zhao
Xiaoli Ma
Haiji Sun
author_facet Zepeng Wang
Xinyu Li
Yuanyuan Li
Xuehan Sun
Yuxue Wang
Tong Lu
Dongqin Zhao
Xiaoli Ma
Haiji Sun
author_sort Zepeng Wang
collection DOAJ
description Previous studies have shown that acute stress-induced gastric mucosal damage is linked to excessive activation of parasympathetic nervous system. The Insular Cortex (IC), the higher centers of the parasympathetic nervous system, serves as both the integration site of gastric sensory information and play a crucial role in the regulation of gastric function. However, whether the IC is involved in Restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of neuronal c-Fos, PSD95 and SYN-1 protein expression in IC during RWIS by immunofluorescence and western blot techniques, as well as assessed IC blood oxygenation level dependant (BOLD) through functional MRI. Chemical genetics techniques specifically modulate the activity of IC glutamatergic neurons and IC-nucleus tractus solitary (NTS) glutamatergic pathway to elucidate their contributions to RWIS-induced gastric mucosal damage. The results showed that the expression of c-Fos, PSD95, and SYN-1 protein in IC increased significantly after RWIS, along with a noticeable enhancement in fMRI signal intensity. Furthermore, inhibiting IC glutamatergic neurons and the IC-NTS glutamatergic neural pathway resulted in a significant reduction in gastric mucosal damage, an increase in the expression of Occludin, Claudin-1, and PCNA in the gastric wall, while the expression of nNOS decreased and CHAT increased. These findings suggest that during RWIS, IC glutaminergic neurons are activated, promoting stress-induced gastric mucosal damage through the IC-NTS-vagal nerve pathway.
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spelling doaj-art-c7dafc11fdfa4501bbdd7d2ec306eed52025-08-20T02:04:43ZengElsevierNeurobiology of Stress2352-28952025-05-013610072310.1016/j.ynstr.2025.100723The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in ratsZepeng Wang0Xinyu Li1Yuanyuan Li2Xuehan Sun3Yuxue Wang4Tong Lu5Dongqin Zhao6Xiaoli Ma7Haiji Sun8Key Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, ChinaKey Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, ChinaKey Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, ChinaKey Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, ChinaKey Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, ChinaResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, ChinaKey Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, ChinaResearch Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, China; Corresponding author. Central Hospital Affiliated to Shandong First Medical University, China.Key Laboratory of Animal Resistance Biology of Shandong Province, School of Life Science, Shandong Normal University, 88# Wenhua Road, Jinan, 250014, China; Corresponding author. Shandong Normal University, China.Previous studies have shown that acute stress-induced gastric mucosal damage is linked to excessive activation of parasympathetic nervous system. The Insular Cortex (IC), the higher centers of the parasympathetic nervous system, serves as both the integration site of gastric sensory information and play a crucial role in the regulation of gastric function. However, whether the IC is involved in Restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of neuronal c-Fos, PSD95 and SYN-1 protein expression in IC during RWIS by immunofluorescence and western blot techniques, as well as assessed IC blood oxygenation level dependant (BOLD) through functional MRI. Chemical genetics techniques specifically modulate the activity of IC glutamatergic neurons and IC-nucleus tractus solitary (NTS) glutamatergic pathway to elucidate their contributions to RWIS-induced gastric mucosal damage. The results showed that the expression of c-Fos, PSD95, and SYN-1 protein in IC increased significantly after RWIS, along with a noticeable enhancement in fMRI signal intensity. Furthermore, inhibiting IC glutamatergic neurons and the IC-NTS glutamatergic neural pathway resulted in a significant reduction in gastric mucosal damage, an increase in the expression of Occludin, Claudin-1, and PCNA in the gastric wall, while the expression of nNOS decreased and CHAT increased. These findings suggest that during RWIS, IC glutaminergic neurons are activated, promoting stress-induced gastric mucosal damage through the IC-NTS-vagal nerve pathway.http://www.sciencedirect.com/science/article/pii/S2352289525000177Insular cortexNucleus tractus solitariusGlutamatergic neuronsGastric mucosal damageRWIS
spellingShingle Zepeng Wang
Xinyu Li
Yuanyuan Li
Xuehan Sun
Yuxue Wang
Tong Lu
Dongqin Zhao
Xiaoli Ma
Haiji Sun
The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats
Neurobiology of Stress
Insular cortex
Nucleus tractus solitarius
Glutamatergic neurons
Gastric mucosal damage
RWIS
title The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats
title_full The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats
title_fullStr The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats
title_full_unstemmed The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats
title_short The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats
title_sort insular cortex nucleus tractus solitarius glutamatergic pathway involved in acute stress induced gastric mucosal damage in rats
topic Insular cortex
Nucleus tractus solitarius
Glutamatergic neurons
Gastric mucosal damage
RWIS
url http://www.sciencedirect.com/science/article/pii/S2352289525000177
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