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Potential rat model of anxiety-like gastric hypersensitivity induced by sequential stress

World Journal of Gastroenterology 2017年第42期23卷 7594-7608页

作者： Fu-Chun Jing Jun Zhang Chen Feng Yuan-Yuan Nian Jin-Hai Wang Hao Hu Bao-De Yang Xiao-Ming Sun Jian-Yun Zheng Xiao-Ran Yin Department of Gastroenterology Second Hospital Affiliated to the Medical School of Xi'an Jiao Tong University Department of Digestive Diseases Baoji People's Hospital Affiliated to the Medical School of Yan'an University Department of Pha-rmacology Health Science CenterXi'an Jiao Tong University Basic Medical Experiment Teaching Center Health Science CenterXi'an Jiao Tong University Department of Pathology the First Affiliated Hospital of Xi'an Medical University

AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential *** Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were *** Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10

关键词： gastric hypersensitivity Anxiety Functional dyspepsia 5-hydroxytryptamine γ-aminobutyric acid Brain-derived neurotrophic factor Nesfatin-1 Rat model

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Ion channel mechanism of gastrointestinal motility and gastric hypersensitivity in functional dyspepsia:a review

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Gastroenterology & Hepatology Research 2022年第3期4卷 23-29页

作者： Terigele Bao Feng Lan Guorui Li Xiyele Mu Ta Na Minghai Fu Yongsheng Chen School of Mongolian Medicine Inner Mongolia University for NationalitiesTongliao 028000Inner Mongolia Autonomous RegionChina School of Life Sciences Inner Mongolia University for NationalitiesTongliao 028000Inner Mongolia Autonomous RegionChina

Functional dyspepsia(FD)is a regularly diagnosed clinical gastrointestinal ailment with a high incidence rate that can considerably impact patients’health and quality of life and impose a substantial financial *** research on the pathophysiology of functional dyspepsia has not thoroughly explained the underlying *** condition does not manifest any significant organ abnormalities,which raises the disease’s difficulty *** pathogenic exceptions in FD include gastrointestinal motor dysfunction,gastrointestinal hormone secretion problem,visceral hypersensitivity,and brain-gut *** ion channels have reportedly been implicated in the pathophysiological process of ***,it is crucial to comprehend the probable activities of various ion channels in *** study focuses on the current state of research on the possible role of several ion channels in the pathogenesis of FD.

关键词： functional dyspepsia ion channel gastrointestinal motility gastric hypersensitivity smooth muscle

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Folic acid treatment alleviates gastric hypersensitivity by regulating DNMT1/ASIC1signal pathway in adult rat offspring following prenatal maternal stress

Folic acid treatment alleviates gastric hypersensitivity by ...

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2019中国生理学会学术年会暨张锡钧基金第十五届全国青年优秀生理学学术论文交流会及第十三届全国青年生理学工作者学术会议

作者：许宇成 Yuan-Qing Tian Yan-Yan Wu Ping-an Zhang Hong-Jun Wang Guang-Yin Xu Institute of Neuroscience Soochow University

Background & Aim: Functional dyspepsia(FD) is a common functional disorder of gastrointestinal *** pathogenesis of visceral pain remains largely *** previous study has demonstrated that prenatal maternal stress(PMS) induced gastric hypersensitivity in adult offspring rats through acid-sensing ion channels(ASICs) protein upregulation and DNA Methyltransferases (DNMTs) downregulation in the level of *** the process of embryonic development, folic acid can prevent neural tube deformity and improve embryonic internal ***, the aim of the present study was to investigate the roles and mechanisms of folic acid on gastric hypersensitivity and to provide a theoretical basis for clinical treatment of chronic visceral ***: Electromyographic(EMG) recording was used to evaluate gastric *** and Western Blotting were performed to detect the expression of ASIC1 and DNMT1 in gastric DRGs of *** cell patch clamp techniques were applied to measure gastric-specific DRG neurons ***: PMS induced gastric hypersensitivity of adult rat offspring in 7 weeks while the ASIC1 protein expression was significantly upregulated and DNMT1 protein expression was greatly *** injection of DNMT1-overexpression lentivirus markedly inhibited the expression of ASIC-1, meanwhile the gastric-specific DRG neurons excitability was significantly reduced in PMS *** importantly, intrathecal injection of DNMT1-overexpression lentivirus attenuated gastric ***, intraperitoneal injection of folic acid markedly reduced the expression of ASIC1 and enhanced DNMT1 protein level,reduced the gastric-specific DRG neurons excitability and alleviated gastric ***: Our data suggest that PMS-induced gastric hypersensitivity in adult rat offspring was associated with increased ASIC1 protein *** acid can alleviate chronic visceral pain in PMS rat by enhancin

关键词： gastric hypersensitivity Dorsal root ganglion Acid-sensing ion channels DNA Methyltransferase Folic acid

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Promoted interaction of nuclear factor-kappa B with demethylated cystathionine-beta-synthetase gene contributes to gastric hypersensitivity in diabetic rats

Promoted interaction of nuclear factor-kappa B with demethyl...

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中国神经科学学会第十届全国学术会议

作者： Hong-Hong ZHANG Ji HU You-Lang ZHOU Shu-Fen HU Yong-Meng WANG Wei CHEN Ying XIAO Li-Yen Mae HUANG Xing-Hong JIANG Guang-Yin XU Division of Endocrinology the Second Affiliated HospitalSoochow University Institute of Neuroscience Suzhou Key Laboratory of Pain Research and TherapyDepartment of NeurobiologySoochow University Department of Neuroscience and Cell Biology University of Texas Medical Branch

Objective The study was designed to determine the role for nuclear factor-kappaB(NF-kappaB) and hydrogen sulfide(HS) signaling pathways in diabetic gastric *** Diabetes were induced by intraperitoneal(i.p.) injection of streptozotocin(STZ,65 mg/kg) in adult female *** responses to graded gastric balloon distention will be employed on normal and diabetic *** clamp recordings were performed in vitro on single gastric-specific DRG neurons acutely isolated from these rats labeled with dye *** of HS producing enzyme Cystathionine- beta-synthetase(CBS) and DNA methyl-transferase(DNMT) were measured with western blotting and real-time PCR *** methylation status were determined by methylation specific PCR and bisulfite *** of cbs gene pairs NF-kappaB was analyzed with chromatin immunoprecipitation ***(1) Diabetic rats were more sensitive to graded gastric balloon distention 4 weeks after STZ treatment(***,Pgastric hyperalgesia.(2) The excitability of gastric-specific DRG neurons from diabetic rats was *** week after *** of AOAA,the neuronal excitability was *** addition,NaHS(donor of HS) increased the excitability of the gastric-specific DRG neurons of normal rats.(3) CBS and CBS mRNA expression of gastric DRGs in diabetic rats was greatly enhanced(Pgastric DRGs contained recognition sequence region of NF-kappaB and was significantly demethylated in diabetic rats(***,Pgastric-specific DRGs in diabetic rats was grea

关键词： diabetes gastric hypersensitivity hydrogen sulfide nuclear factor-kappaB DNA methylation

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Epigenetic Upregulation of Acid-sensing Ion Channel 1 Contributes to gastric hypersensitivity in Adult Offspring Rats With Prenatal Maternal Stress

Epigenetic Upregulation of Acid-sensing Ion Channel 1 Contri...

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中国神经科学学会第十二届全国学术会议

作者： Hong-Jun Wang Xue Xu Meng Li Guang-Yin Xu Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-PsychoDiseases Institute of Neuroscience Soochow University Jiangsu Key Laboratory of Anesthesiology & Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology Xuzhou Medical University

Objective Functional dyspepsia is one of the most common functional gastrointestinal disorders. gastric hypersensitivity（GHS） is a hallmark of this disorder but the etiology and cellular mechanisms remain largely unknown. Stressors during gestational period could have effect on the offspring’s tissue structure and function, which may predispose to gastrointestinal diseases. The aim of this study was to investigate whether prenatal maternal stress（PMS） could affect GHS and roles of nuclear factor-κB（NF-κB）/acid-sensing ion channel（ASIC） signaling pathway in the development and maintenance of GHS. Methods GHS in response to gastric balloon distention was examined by electromyographic recordings. Changes in neuronal excitability were determined by whole-cell patch-clamp recording techniques. Demethylation of Cp G islands of asic1 gene was determined by methylation-specific PCR. Results PMS produced GHS in adult offspring. Amiloride, an ASIC inhibitor, significantly attenuated GHS and reversed hyperexcitability of gastric-specific dorsal root ganglion（DRG） neurons labeled by the dye Di I. Expression of ASIC1 and p65 were markedly enhanced in gastric DRGs. Furthermore, PMS led to a significant demethylation of Cp G islands in the asic1 gene promoter region. PMS also enhanced the ability of asic1 to bind DNA at the p65 consensus site. Blockade of NF-κB using lentiviral-p65 sh RNA reversed upregulation of ASIC1, GHS and hyperexcitability of DRG neurons. Conclusion These data suggest that upregulation of asic1 expression is attributed to asic1 promoter DNA demethylation and p65 activation and that the enhanced interaction of the asic1 gene and p65 contributes to GHS induced by PMS.

关键词： gastric hypersensitivity Prenatal maternal stress Dorsal root ganglion Acid-sensing ion channel Epigenetics

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