Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that th...Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.展开更多
Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in ...Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract.Berberine,an isoquinoline alkaloid,is known as its antiinflammatory and therapeutic effects in experimental colitis.However,little research focused on its regulatory function on ENS.Therefore,we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions.Functional defects of enteric glial cells(EGCs),with decreased glial fibrillary acidic protein(GFAP)and increased substance P expression,were observed in DSS-induced murine UC.Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC,closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation.In vitro,berberine showed direct protective effects on monoculture of EGCs,bone marrowderived dendritic cells(BMDCs),T cells,and intestinal epithelial cells(IECs)in the simulated inflammatory conditions.Furthermore,berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems.In summary,our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.展开更多
目的:观察针刺对便秘模型大鼠肠神经系统神经元标志物PGP9.5表达的影响.方法:将60只大鼠按照体质量及随机分组.正常对照组15只,45只大鼠予生大黄水煎液灌胃,开始用量为100g/(kg?d),最后为1280g/(kg?d),45d后造模36只,治疗前处死12只作...目的:观察针刺对便秘模型大鼠肠神经系统神经元标志物PGP9.5表达的影响.方法:将60只大鼠按照体质量及随机分组.正常对照组15只,45只大鼠予生大黄水煎液灌胃,开始用量为100g/(kg?d),最后为1280g/(kg?d),45d后造模36只,治疗前处死12只作为造模末治疗前组对照,剩余随机分为针刺组和空白治疗组,各12只.针刺组大鼠针刺天枢和足三里,天枢加电针,疏密波刺激10min,每日1次,共计14d;空白治疗组不给予治疗.2组14d后处死,取距离肛门5cm肠管,用HE染色和PGP9.5免疫组织化学染色,采用Image-Pro Plus 5.0计算各组PGP9.5的综合吸光度值(IA值)分析肠神经节细胞的状况.结果:正常组PGP9.5表达的IA值(×104)为47.38±9.04,治疗前组为20.36±9.12,2组比较有显著差异(P<0.000);空白组为28.51±9.43,与治疗前组比较无统计学差异(P>0.05);针刺组为41.39±19.56,与治疗前组和空白组比较均有统计学差异(均P<0.05),与正常组比较无统计学差异(P>0.05).结论:针刺有助于改善大黄水煎液灌胃泻剂便秘模型大鼠神经节细胞功能.展开更多
Cajal间质细胞(interstitial cells of Cajal,ICC)是胃肠慢波的起搏细胞,具有产生慢波、传导慢波电位、调节神经递质等功能,是调节胃肠动力的重要环节。ICC在维持正常胃肠动力方面发挥着重要作用,同时其形态、数量及分布的改变会导致多...Cajal间质细胞(interstitial cells of Cajal,ICC)是胃肠慢波的起搏细胞,具有产生慢波、传导慢波电位、调节神经递质等功能,是调节胃肠动力的重要环节。ICC在维持正常胃肠动力方面发挥着重要作用,同时其形态、数量及分布的改变会导致多种胃肠动力障碍性疾病。一些以ICC为靶向治疗胃肠动力性疾病药物的研究也取得一定进展。本文就近年来ICC与胃肠动力关系的研究进展作一概述。展开更多
In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called ...In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.展开更多
文摘Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.
基金supported by Science and Technology Commission of Shanghai Municipality,China(No.18431907100)technical assistance from the Platform of Molecular Imaging and Research,SIMM,CAS,Beijing,China.
文摘Ulcerative colitis(UC)manifests as an etiologically complicated and relapsing gastrointestinal disease.The enteric nervous system(ENS)plays a pivotal role in rectifying and orchestrating the inflammatory responses in gut tract.Berberine,an isoquinoline alkaloid,is known as its antiinflammatory and therapeutic effects in experimental colitis.However,little research focused on its regulatory function on ENS.Therefore,we set out to explore the pathological role of neurogenic inflammation in UC and the modulating effects of berberine on neuro-immune interactions.Functional defects of enteric glial cells(EGCs),with decreased glial fibrillary acidic protein(GFAP)and increased substance P expression,were observed in DSS-induced murine UC.Administration of berberine can obviously ameliorate the disease severity and restore the mucosal barrier homeostasis of UC,closely accompanying by maintaining the residence of EGCs and attenuating inflammatory infiltrations and immune cells overactivation.In vitro,berberine showed direct protective effects on monoculture of EGCs,bone marrowderived dendritic cells(BMDCs),T cells,and intestinal epithelial cells(IECs)in the simulated inflammatory conditions.Furthermore,berberine could modulate gut EGCs-IECs-immune cell interactions in the co-culture systems.In summary,our study indicated the EGCs-IECs-immune cell interactions might function as a crucial paradigm in mucosal inflammation and provided an infusive mechanism of berberine in regulating enteric neurogenic inflammation.
文摘目的:观察针刺对便秘模型大鼠肠神经系统神经元标志物PGP9.5表达的影响.方法:将60只大鼠按照体质量及随机分组.正常对照组15只,45只大鼠予生大黄水煎液灌胃,开始用量为100g/(kg?d),最后为1280g/(kg?d),45d后造模36只,治疗前处死12只作为造模末治疗前组对照,剩余随机分为针刺组和空白治疗组,各12只.针刺组大鼠针刺天枢和足三里,天枢加电针,疏密波刺激10min,每日1次,共计14d;空白治疗组不给予治疗.2组14d后处死,取距离肛门5cm肠管,用HE染色和PGP9.5免疫组织化学染色,采用Image-Pro Plus 5.0计算各组PGP9.5的综合吸光度值(IA值)分析肠神经节细胞的状况.结果:正常组PGP9.5表达的IA值(×104)为47.38±9.04,治疗前组为20.36±9.12,2组比较有显著差异(P<0.000);空白组为28.51±9.43,与治疗前组比较无统计学差异(P>0.05);针刺组为41.39±19.56,与治疗前组和空白组比较均有统计学差异(均P<0.05),与正常组比较无统计学差异(P>0.05).结论:针刺有助于改善大黄水煎液灌胃泻剂便秘模型大鼠神经节细胞功能.
文摘Cajal间质细胞(interstitial cells of Cajal,ICC)是胃肠慢波的起搏细胞,具有产生慢波、传导慢波电位、调节神经递质等功能,是调节胃肠动力的重要环节。ICC在维持正常胃肠动力方面发挥着重要作用,同时其形态、数量及分布的改变会导致多种胃肠动力障碍性疾病。一些以ICC为靶向治疗胃肠动力性疾病药物的研究也取得一定进展。本文就近年来ICC与胃肠动力关系的研究进展作一概述。
文摘In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called "functional" or "idiopathic" disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of "functional" gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors' work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.
