Maturation and development of fetal pig intestinal tissue in immunodeficient mice

Purpose: This study aimed to compare the degree of maturation and development of fetal pig segmental intestinal tissue with that of spheroids created by in-vitro reaggregation of dissociated fetal intestinal cells after transplantation into immunodeficient mice. Methods: Fetal pig small intestines were transplanted as segmental grafts into the omentum and subrenal capsules of immunodeficient mice or enzymatically treated to generate single cells. Spheroids made by in-vitro reaggregation of these cells were transplanted into the subrenal capsules of immunodeficient mice. The segmental grafts and spheroids were harvested four and eight weeks after transplantation, and the structural maturity and in-vivo development of these specimens were histologically evaluated. Results: The spheroids were engrafted and supplied blood vessels from the host mice, but an intestinal layered structure was not clearly observed, and there was almost no change in size. On the other hand, the segmental grafts formed deep crypts in the mucus membrane, the inner circular layer, and outer longitudinal muscles. The crypts of the transplanted grafts harvested at eight weeks were much deeper, and the smooth muscle layer and the enteric nervous system were more mature than those of grafts harvested at the fourth week, although the intestinal peristaltic wave was not observed. Conclusions: Spheroids created from fetal small intestinal cells could not form layered structures or mature sufficiently. Conversely, segmental tissues structurally matured and developed after in-vivo transplantation and are therefore potential grafts for transplantation.

Papel de la plasticidad celular en la regeneración intestinalinducida por lesiones / Role of cell plasticity in injury-induced intestinal regeneration

El sistema intestinal posee una capacidad regenerativa intrínseca y fisiológica que tiene lugar a partir de las células madreLgr5+ ubicadas en el fondo de las criptas intestinales, las cuales se diferencian hacia las células progenitoras secretoras y absortivas con sus respectivas células especializadas mediante la activación de señalizaciones intracelulares como Wnt, Hippo y Notch. Condiciones adversas como lesiones e infecciones tisulares inducen esta actividad regenerativa promovida por variados mecanismos que influyen en el microambiente celular. El sistema inmunológico detecta alteraciones en el tejido intestinal y, a través de la activación de células inmunocompetentes y la secreción de citoquinas proinflamatorias, favorece la desdiferenciación de células especializadas hacia células madre para desencadenar la respuesta regenerativa. En cuanto al sistema nervioso entérico, su influencia está sujeta a modificaciones en la microbiota y los hábitos alimenticios, y se encuentra determinada en gran parte, por las células gliales entéricas y la expresión de distintos marcadores de plasticidad, que permiten limitar la lesión y reparar el tejido. Por su parte, la epigenéticamodifica la expresión genética y consecuentemente, la capacidadregenerativa intestinal, variando de acuerdo a cada paciente porla influencia de factores externos como la dieta o el estadopsicobiológico. De esta forma, la respuesta regenerativa intestinalinducida por lesiones, integra múltiples mecanismos y poseeimportantes repercusiones clínicas en cuanto a EII, disbiosise incluso tumorogénesis; conocer los mecanismos que regulanesta actividad puede sentar las bases para la creación de terapias innovadoras en el mismo ámbito(AU)

The intestinal system has an intrinsic and physiological regenerative capacity that takes place from the Lgr5+ stem cells located at the bottom of the intestinal crypts, which differentiate into secretory and absorptive progenitor cells with their specialized cells by activating intracellular signalslike Wnt, Hippo and Notch. Adverse conditions such asinjuries and tissue infections induce this regenerative activity promoted by various mechanisms that influence the cellular microenvironment. The immune system senses disturbances in the intestinal tissue and, through the activation of immunocompetent cells and the secretion of proinflammatorycytokines, favors the dedifferentiation of specialized cells intostem cells to trigger the regenerative response. Regarding theenteric nervous system, its influence is subject to modificationsin the microbiota and dietary habits, and is largely determinedby enteric glial cells and the expression of different plasticitymarkers, which enable to limit injuries and repair tissue. On the other hand, epigenetics modifies genetic expressionand, consequently, intestinal regenerative capacity, varying according to each patient due to the influence of external factors such as diet or psychobiological status. There fore, the intestinal regenerative response induced by lesions integrates multiple mechanisms and has important clinical repercussions in terms of IBD, dysbiosis, and even tumorigenesis; knowing themechanisms that regulate this activity can lay the foundations for the creation of innovative therapies in the same field (AU)

Ganglioneuromatosis intestinal difusa a lo largo del tubo digestivo / Diffuse intestinal ganglioneuromatosis along the gastrointestinal tract

Resumen Introducción: Los ganglioneuromas son neoplasias histológicamente benignas derivadas del sistema nervioso simpático, cuya ocurrencia en el tubo digestivo es rara y comúnmente sindromática. De acuerdo con el patrón de la lesión y la extensión se dividen en ganglioneuroma polipoide, poliposis ganglioneuromatosa y ganglioneuromatosis difusa. El objetivo de este trabajo es presentar el hallazgo incidental post mortem de ganglioneuromatosis difusa del tubo digestivo en una paciente sin afectación sindromática. Caso clínico: Se describe el caso de un paciente de sexo femenino de 2 años con atresia traqueoesofágica tipo III corregida quirúrgicamente que cursó con recanalización fistulosa, múltiples episodios de neumonía por aspiración y choque séptico. Durante el último ingreso cursó con hemorragia pulmonar masiva y falla multiorgánica. En el estudio post mortem se identificó hipertrofia del píloro y de los troncos y plexos nerviosos entéricos con células ganglionares maduras entremezcladas. Se identificó ganglioneuromatosis que afectaba todos los segmentos del tubo digestivo, con predominio de los plexos mientéricos. Conclusiones: La ganglioneuromatosis intestinal es una rara enfermedad que presenta un espectro de lesiones desde una forma aislada hasta sindromática con morbimortalidad elevada. Por ello, es necesario conocer la enfermedad, indagar sistemáticamente cuando se sospeche y apoyarse de estudios genéticos que confirmen o descarten alguna asociación sindromática.

Abstract Background: Ganglioneuromas are histologically benign neoplasms derived from the sympathetic nervous system, whose occurrence in the gastrointestinal tract is rare and often syndromic. According to the injury pattern and extension, lesions are divided into polypoid ganglioneuroma, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. This work aimed to present the incidental post mortem finding of diffuse ganglioneuromatosis of the gastrointestinal tract in a patient without syndromic involvement. Case report: We describe the case of a two-year-old female patient with surgically corrected type III tracheoesophageal atresia and fistulous recanalization, multiple episodes of aspiration pneumonia, and septic shock. During the last admission, she developed massive pulmonary hemorrhage and multi-organ failure. Post mortem histopathological study identified hypertrophy of the pylorus and enlarged enteric nerve trunks and plexuses with intermingled mature ganglion cells. We identified ganglioneuromatosis affecting all gastrointestinal tract segments with the predominance of the myenteric plexuses. Conclusions: Intestinal ganglioneuromatosis is a rare disease with a spectrum of lesions ranging from isolated to syndromic with high morbidity and mortality. Therefore, it is necessary to know the condition, investigate systematically when it is suspected, and rely on genetic studies to confirm or rule out any syndromic association.

Location, distribution, and quantification of myenteric plexus neurons of the jejunum of quails fed with different levels of commercial Macleaya cordata extract / Localização, distribuição e quantificação dos neurônios do plexo mioentérico do jejuno de codornas de postura alimentadas com diferentes inclusões do extrato comercial de Macleaya cordata

ABSTRACT: Coturniculture has been promising, progressing from a subsistence to a technical activity due to its quick production, low breeding investment, and rapid economic return. After the restriction of antimicrobials as growth promoters, some studies aimed to evaluate alternative products that would make the farming of healthy birds viable without impacting their performance, with commercial Macleaya cordata extract being one of these substitutes. The functions of the gastrointestinal tract are coordinated mainly by the enteric nervous system, and the myenteric plexus is responsible for the reflex control of contractile activities of the external muscles. Thus, this study located and demonstrated the distribution of the myenteric plexus, quantifing the total population of myenteric neurons (Giemsa+) and the subpopulation of myenteric nitrergic neurons (NADPH-d+), and evaluated the effects of commercial Macleaya cordata extract on these populations of quail jejunum neurons. A total of 240 one-day-old female laying quails were distributed into four treatments, with four repetitions of 15 birds each. The test groups (T1, T2, and T3) were treated with commercial Macleaya cordata extract throughout the experimental period using the following doses: T1 - test group, basal diet added with 150 ppm of the extract in the feed; T2- test group, basal diet added with100 ppm of the extract in the feed; T3 - test group, basal diet added with 50 ppm of the extract in the feed; and T4 - control group, basal diet with no added extract. The study included histological analysis, Giemsa+, and NADPH-d+ myenteric neuron staining. The results showed that the myenteric plexus is located between longitudinal layer fibers and in the transition region between the longitudinal and circular layers of the muscular tunic, with the myenteric population organized into ganglia and isolated in the region of neuronal fiber bundles. The commercial Macleaya cordata extract showed no quantitative changes in the myenteric Giemsa+ population and myenteric NADPH-d+ subpopulation, however, the groups that consumed the extract showed greater NADPH-d+ neuron activity compared to the control group, implying that the food remained longer in the intestinal lumen, therefore, enabling greater nutrient use and resulting in increased productive performance.

RESUMO: A coturnicultura tem apresentado características promissoras, deixando de ser uma atividade de subsistência e ocupando patamares tecnificados devido a sua precocidade produtiva, baixo investimento de criação e rápido retorno econômico. A partir da restrição da utilização de antimicrobianos como promotores de crescimento, estudos foram direcionados com o objetivo de se avaliar produtos alternativos que viabilizassem a criação de aves saudáveis, sem comprometer seu desempenho, sendo o extrato comercial da Macleaya cordata um destes substitutos. As funções do trato gastrintestinal são coordenadas principalmente pelo sistema nervoso entérico, sendo o plexo mioentérico responsável pelo controle reflexo das atividades contráteis da musculatura externa. Desta forma, o presente trabalho teve como objetivo localizar e demonstrar a distribuição do plexo mioentérico, quantificar a população total de neurônios mioentéricos (Giemsa+), e a subpopulação de neurônios mioentéricos nitrérgicos (NADPH-d+), além de avaliar os efeitos do extrato comercial da Macleaya cordata sobre estas populações de neurônios do jejuno de codornas. Foram alojadas 240 codornas de postura, fêmeas, com um dia de idade, distribuídas aleatoriamente em quatro tratamentos, com quatro repetições de 15 aves cada. Os grupos testes (T1, T2 e T3) foram tratados com extrato comercial de Macleaya cordata durante todo o período experimental conforme as doses indicadas, sendo: T1 - grupo teste, com dieta basal adicionada de 150 ppm do extrato na ração; T2 - grupo teste, com dieta basal adicionada de 100 ppm do extrato na ração; T3 - grupo teste, com dieta basal adicionada de 50 ppm do extrato na ração, e T4 - grupo controle, com dieta basal isenta do extrato. Foram realizadas análise histológica e a marcação dos neurônios mioentéricos Giemsa+ e NADPH-d+. Os resultados demonstraram que o plexo mioentérico está localizado entre as fibras do estrato longitudinal, e na região de transição entre os estratos longitudinal e circular da túnica muscular, estando a população mioentérica organizada em gânglios, e também isoladamente na região dos feixes das fibras neuronais. O extrato comercial da Macleaya cordata não alterou quantitativamente os neurônios da população mioentérica Giemsa+ e da subpopulação mioentérica NADPH-d+, mas os grupos que consumiram o extrato apresentaram maior atividade dos neurônios NADPH-d+ em relação ao grupo controle, permitindo inferir que o alimento permaneceu maior tempo no lúmen intestinal e, portanto, possibilitou um maior aproveitamento dos nutrientes, podendo refletir em melhor desempenho produtivo.

Sarm1-mediated neurodegeneration within the enteric nervous system protects against local inflammation of the colon

Axonal degeneration is one of the key features of neurodegenerative disorders. In the canonical view, axonal degeneration destructs neural connections and promotes detrimental disease defects. Here, we assessed the enteric nervous system (ENS) of the mouse, non-human primate, and human by advanced 3D imaging. We observed the profound neurodegeneration of catecholaminergic axons in human colons with ulcerative colitis, and similarly, in mouse colons during acute dextran sulfate sodium-induced colitis. However, we unexpectedly revealed that blockage of such axonal degeneration by the Sarm1 deletion in mice exacerbated the colitis condition. In contrast, pharmacologic ablation or chemogenetic inhibition of catecholaminergic axons suppressed the colon inflammation. We further showed that the catecholaminergic neurotransmitter norepinephrine exerted a pro-inflammatory function by enhancing the expression of IL-17 cytokines. Together, this study demonstrated that Sarm1-mediated neurodegeneration within the ENS mitigated local inflammation of the colon, uncovering a previously-unrecognized beneficial role of axonal degeneration in this disease context.

Quantification of the neurons of myenteric plexus of the bat molossus rufus / Quantificação dos neurônios do plexo mientérico de morcegos da espécie Molossus rufus

There are no studies that characterize the enteric nervous system (ENS) bats. The organization and density of myenteric neurons may vary according to the animal species, as well as the segment of the digestive tube considered. The nitric oxide is one of the key neurotransmitters present in the myenteric neurons, acting as a mediator in the smooth muscle relaxation. These neurons are evidenced by immunohistochemistry of nitric oxide synthase (NOS) or by NADPH-diaphorase histochemistry. In this sense, this study aimed to characterize the total neuronal population and subpopulation NADPH-d+ of the myenteric plexus present in the jejunum of the insectivore species Molossus rufus quantitatively. Five specimens were collected of M. rufus in a buffer area of the "Reserva Biológica das Perobas" in the microregion of Cianorte/PR. After the euthanasia, in a chamber saturated with isoflurane, segments were collected from the small intestine corresponding to the jejunum intended for two techniques for neuronal marking, Giemsa and NADPH-diaphorase, and a fragment to the histological technique of hematoxylin-eosin and Masson's trichrome. All the procedures were approved by the "Comitê de Ética no Uso de Animais Unipar" (CEUA - protocol No. 34347/2017) and the "Instituto Chico Mendes de Conservação da Biodiversidade" (ICMBio - protocol No. 60061-1) The histological sections allowed to highlight the location of the myenteric plexus between the longitudinal and circular layers of the muscular tunic. The myenteric plexus had an average of total neuronal population (neurons Giemsa+) of 279.23 neurons/mm2, being the nitrergic neurons (neurons NADPH-d+) represented 20.4% of this total population, with an average of 58.14 neuron/mm2. Therefore, the collected data are consistent with previous studies in other mammalian species concerning the location of the myenteric plexus, as well as the neural myenteric proportion NADPH-d+ compared with the population of neurons Giemsa+. The gaps in the knowledge of ENS of bats limits comparative intraspecific and interspecific studies.(AU)

Não há estudos que caracterizem o sistema nervoso entérico (SNE) destes animais, configurando uma lacuna no conhecimento quanto à biologia destes indivíduos. A organização e densidade dos neurônios mientéricos podem variar de acordo com a espécie animal bem como o segmento do tubo digestório considerado. O óxido nítrico é um dos principais neurotransmissores presentes nos neurônios mientéricos, atuando como mediador no relaxamento do músculo liso gastrointestinal, de modo que estes neurônios são evidenciados igualmente pela imunohistoquímica da óxido nítrico-sintase (NOS) ou pela histoquímica da NADPH-diaforase. Neste sentido, objetivou-se caracterizar quantitativamente a população neuronal total e subpopulação NADPH-d+ do plexo mientérico presente no jejuno da espécie Molossus rufus de hábito alimentar insetívoro. Foram coletados cinco espécimes de M. rufus em área de amortecimento da Reserva Biológica das Perobas na microrregião de Cianorte/PR. Após a eutanásia, em câmara saturada com isoflurano, foram coletados segmentos do intestino delgado correspondentes ao jejuno destinados a duas técnicas para marcação neuronal, Giemsa e NADPH-diaforase e, um fragmento para a técnica histológica de hematoxilina-eosina e tricômio de Masson. Todos os procedimentos realizados foram aprovados pelo Comitê de Ética no Uso de Animais da Unipar (CEUA - protocolo nº 34347/2017) e pelo Instituto Chico Mendes de Conservação da Biodiversidade (ICMBio - protocolo nº 60061-1) Os cortes histológicos possibilitaram evidenciar a localização do plexo mientérico entre os estratos longitudinal e circular da túnica muscular. Neurônios Giemsa+ apresentaram uma média de 279,23 neurônios/mm2, já os neurônios nitrérgicos apresentaram em média 20,4% da população neuronal mientérica total, sendo evidenciados 58,14 neurônios NADPH-d+/mm2. Portanto, os dados coletados mostram-se condizentes com estudos anteriores em outras espécies de mamíferos quanto à localização do plexo mientérico, bem como, a proporção neuronal mientérica NADPH-d+ comparada com a população de neurônios Giemsa+. As lacunas existentes quanto ao conhecimento do SNE de morcegos limita possíveis inferências em comparativo intraespecífico e interespecífico.(AU)

Advances in Study on Pathogenesis of Irritable Bowel Syndrome / 胃肠病学

The pathophysiological process of irritable bowel syndrome (IBS) is complex. Recent studies showed that alteration in gut microbiota, damage of intestinal mucosal barrier and increase of mucosal permeability due to inflammation, diet and stress, as well as abnormalities of enteric nervous system in both function and morphology play important roles in the development of IBS. In this article, the advances in studies on above mentioned pathogenic mechanisms of IBS were briefly summarized.

Study on Dose-effect Relationship and Mechanism of Protective Effects of Total Asiaticoside on Gastrointestinal Motility and Enteric Nervous System in Aged Functional Dyspepsia Model Rats / 中国药房

OBJECTIVE：To explo re the dose-effect relationship and mechanism of protective effects of total asiaticoside （TA） on gastrointestinal motility and enteric nervous system （ENS）in aged functional dyspepsia （FD）model rats. METHODS ：Aged male SD rats of 16 months old were randomly divided into blank control group ，model group ，TA low dose ，medium dose and high dose groups （15，30，60 mg/kg），with 8 rats in each group. FD model was established by tail-stimulation combined with irregular diet for 4 weeks. The next day after modeling ，administration groups were given relevant doses of TA solution intragastrically ； control group and model group were given constant volume of normal saline intragastrically ，once a day ，for consecutive 15 d. Gastric emptying rate and small intestinal propulsion rate of rats were examined. ELISA were used to detect serum contents of MTL and VIP. Immunofluorescence and immunohistochemistry were proposed to measure the expression of ENS marker （S100β and GDNF）in gastric antrum tissue. The protein expression of S 100β，GFAP，PGP9.5，GDNF，p-MEK and p-ERK 1/2 in gastric antrum tissue were measured by Western blotting assay. RESULTS ：Compared with blank control group ，gastric emptying rate and small intestinal propulsion rate ，serum MTL content and protein expression of PGP 9.5 in gastric antrum tissue of model and TA low，medium dose group were decreased significantly ，while serum VIP content ，protein expressions of S 100β，GFAP，GDNF， p-MEK and p-ERK 1/2 in gastric tissue were increased significantly （P＜0.05）. Compared with model group ，gastric emptying rate and small intestinal propulsion rate of TA groups were increased significantly （P＜0.05）；except for GFAP protein in TA low dose group（P＞0.05），the serum MTL content and the expression of PGP 9.5 protein in gastric antrum tissue of rats in TA groups were increased significantly ，while serum VIP content ，protein expression of S 100β，GFAP，GDNF，p-MEK and p-ERK 1/2 in gastric antrum tissue were decreased significantly （P＜0.05）. Some or most of the content of gastrointestinal motility indexes and related factor protein expression were significantly different among TA groups （P＜0.05），and the indexes in TA high dose group could recover to the levels which were not significantly different with blank control group （P＞0.05）. CONCLUSIONS ：TA can dose-dependently improve the gastrointestinal motility deficiency and ENS dysfunction in aged FD model rats ，especially in high dose（60 mg/kg）of TA group. Its mechanism may be related with promoting the release of endogenous MTL ，inhibiting the secretion of VIP ，expression of GDNF and the activation of downstream signaling pathway ，and promoting the repair of ENS and intestinal neurons.

A artrite reumatoide afeta o sistema nervoso entérico? / Does the rheumatoid arthritis affect the enteric nervous system?

ABSTRACT BACKGROUND: Few studies regarding arthritic diseases have been performed to verify the presence of the neurodegeneration. Given the increased oxidative stress and extra-articular effects of the rheumatoid arthritis, the gastrointestinal studies should be further investigated aiming a better understanding of the systemic effects the disease on enteric nervous system. OBJECTIVE: To determine whether the rheumatoid arthritis affects the nitrergic density and somatic area of the nNOS- immunoreactive (IR) myenteric neurons, as well as the morphometric areas of CGRP and VIP-IR varicosities of the ileum of arthritic rats. METHODS: Twenty 58-day-old male Holtzmann rats were distributed in two groups: control and arthritic. The arthritic group received a single injection of the Freund's Complete Adjuvant in order to induce arthritis model. The whole-mount preparations of ileum were processed for immunohistochemistry to VIP, CGRP and nNOS. Quantification was used for the nitrergic neurons and morphometric analyses were performed for the three markers. RESULTS: The arthritic disease induced a reduction 6% in ileal area compared to control group. No significant differences were observed in nitrergic density comparing both groups. However, arthritic group yielded a reduction of the nitrergic neuronal somatic area and VIP-IR varicosity areas. However, an increase of varicosity CGRP-IR areas was also observed. CONCLUSION: Despite arthritis resulted in no alterations in the number of nitrergic neurons, the retraction of ileal area and reduction of nitrergic somatic and VIP-IR varicosity areas may suggest a negative impact the disease on the ENS.

RESUMO CONTEXTO: Poucos estudos sobre doenças artríticas têm sido realizados para verificar a presença de neurodegeneração. Diante do aumento do estresse oxidativo e dos efeitos extra-articulares da artrite reumatoide, estudos gastrointestinais devem ser investigados visando uma melhor compreensão dos efeitos sistêmicos da doença no sistema nervoso entérico. OBJETIVO: Determinar se a artrite reumatoide afeta a densidade nitrérgica e a área somática dos neurônios mioentéricos imunorreativos ao nNOS (nNOS-IR), bem como para as áreas morfométricas das varicosidades CGRP-IR e VIP-IR do íleo de ratos artríticos. MÉTODOS: Vinte ratos Holtzmann, com 58 dias de idade, foram distribuídos em dois grupos: controle e artrítico. O grupo artrítico recebeu uma única injeção do adjuvante completo de Freund para induzir o modelo de artrite. Os preparados totais de íleo foram processados para imuno-histoquímica ao VIP, CGRP e nNOS. A quantificação foi utilizada para os neurônios nitrérgicos e as análises morfométricas foram realizadas para os três marcadores. RESULTADOS: A doença artrítica induziu uma redução de 6% na área ileal em relação ao grupo controle. Não foram observadas diferenças significativas na densidade nitrérgica comparando os dois grupos. No entanto, o grupo artrítico produziu uma redução da área somática neuronal nitrérgica e da área das varicosidades do VIP-IR. Entretanto, foi observado um aumento das áreas das viricosidades CGRP-IR. CONCLUSÃO: Apesar da artrite não resultar em alterações no número de neurônios nitrérgicos, a retração da área ileal e a redução das áreas somática nitrérgica e das varicosidades do VIP-IR podem sugerir um impacto negativo da doença no sistema nervoso entérico.

Nervous Mechanism of Gastric Mucosal Lesion Induced by Restraint Water-immersion Stress in Rats / 胃肠病学

Stress-induced gastric mucosal lesion (SGML) is one of the most common visceral complications after trauma. Restraint water-immersion stress (RWIS) can induce gastric mucosal lesion within a few hours. It has been confirmed that hyperfunction of parasympathetic nervous system contributes to the gastric dysfunction induced by RWIS. The dorsal motor nucleus of vagus, nucleus of solitary tract, hypothalamic supraoptic nucleus, paraventricular nucleus, mediodorsal thalamic nucleus, central amygdaloid nucleus and medial prefrontal cortex are all involved in the formation of SGML. Neurotransmitter/neuromodulation such as substance P, acetylcholine, oxytocin may be involved in the physiological process. This article reviewed the nervous mechanism of gastric mucosal lesion induced by RWIS in rats.

Advances on distribution and function of aquaporin 1 in the peripheral nervous system / 第二军医大学学报

Aquaporin 1 (AQP1) is an aquaporin distributed in the peripheral nervous system. It has been found in neurons and glial cells of peripheral nerve structures, including trigeminal ganglion, dorsal root ganglion and enteric nervous system. AQP1 may be involved in the regulation of water balance of ganglia and nerve fiber bundles in the peripheral nervous system under physiological and pathological conditions, and plays a key role in maintaining the intracellular and extracellular water balance of peripheral nervous system under pathological condition. Knowing the structure and function of AQP1 can contribute to the understanding of the pathophysiology of the nervous system, providing new ways and methods for clinical treatment. This review summarizes the recent researches on AQP1.

Diagnosis and treatment of chronic intestinal pseudo-obstruction / 中国实用外科杂志

Chronic intestinal pseudo-obstruction(CIPO)is a rare but serious intestinal dyskinesia characterized by impaired bowel motor function in the absence of mechanical intestinal obstruction. CIPO may be caused by primary and secondary factors that damage the enteric nervous system(neuropathy),smooth muscle(myopathy),and/or Cajal interstitial cells(interstitial disease). CIPO is extremely easy to missed diagnosis and misdiagnosis.The treatment of CIPO is very difficult.It is based on nutritional support,medicine and surgical treatment.At present,the occurrence,development and treatment of intestinal micro-ecology in CIPO has gradually attracted attention and may become a new treatment method for CIPO.

Pyridostigmine in Pediatric Intestinal Pseudo-obstruction: Case Report of a 2-year Old Girl and Literature Review

Pediatric chronic intestinal pseudo-obstruction is a rare disorder characterized by a severe impairment of gastrointestinal motility leading to intestinal obstruction symptoms in the absence of mechanical causes. The diagnosis is usually clinical and diagnostic work is usually aimed to rule out mechanical obstruction and to identify any underlying diseases. Treatment is challenging and requires a multidisciplinary effort. In this manuscript we describe the youngest child successfully treated with the orally administrable, long-acting, reversible anti-cholinesterase drug, pyridostigmine. Like other drugs belonging to cholinesterase inhibitors, pyridostigmine enhances gut motility by increasing acetylcholine availability in the enteric nervous system and neuro-muscular junctions. Based on the direct evidence from the reported case, we reviewed the current literature on the use of pyridostigmine in severe pediatric dysmotility focusing on intestinal pseudo-obstruction. The overall data emerged from the few published studies suggest that pyridostigmine is an effective and usually well tolerated therapeutic options for patients with intestinal pseudo-obstruction. More specifically, the main results obtained by pyridostigmine included marked reduction of abdominal distension, reduced need of parenteral nutrition, and improvement of oral feeding. The present case and review on pyridostigmine pave the way for eagerly awaited future randomized controlled studies testing the efficacy of cholinesterase inhibitors in pediatric severe gut dysmotility.

Does Parkinson's disease start in the gut? / A doença de Parkinson começa no intestino?

ABSTRACT Current understanding of the pathophysiology of Parkinson's disease suggests a key role of the accumulation of alpha-synuclein in the pathogenesis. This critical review highlights major landmarks, hypotheses and controversies about the origin and progression of synucleinopathy in Parkinson's disease, leading to an updated review of evidence suggesting the enteric nervous system might be the starting point for the whole process. Although accumulating and compelling evidence favors this theory, the remaining knowledge gaps are important points for future studies.

RESUMO O atual entendimento sobre a fisiopatologia da doença de Parkinson (DP) sugere um papel central do acúmulo de alfa-sinucleína na patogenia da DP Esta revisão crítica revisita marcos, teorias e controvérsias a respeito da origem e progressão da sinucleinopatia, apresentando uma atualização das principais evidências sugerindo que o sistema nervoso entérico seria o local inicial deste processo. Apesar das evidências a favor desta teoria serem crescentes e instigantes, as lacunas de conhecimento a este respeito são importantes pontos para estudos futuros.

Relation of Enteric α-Synuclein to Gastrointestinal Dysfunction in Patients With Parkinson's Disease and in Neurologically Intact Subjects

BACKGROUND/AIMS: α-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson’s disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk. METHODS: A total of 35 PD patients and 52 neurologically intact subjects were enrolled in this study. Endoscopic biopsies were performed, and then immunohistochemical staining for αSYN was performed. All subjects completed the validated Rome III questionnaire for the assessment of GI symptoms. The association between GI symptoms and the αSYN pathology in GI mucosa was evaluated. Incident PD cases were assessed during a median follow-up of 46 months. RESULTS: The proportion of self-reported constipation and functional constipation through the Rome III questionnaire was significantly higher in PD patients than in controls (P 0.05). No incident PD cases were diagnosed during study period. CONCLUSIONS: Our present study suggests that the deposition of αSYN in the mucosal enteric nervous system may not be reflected by functional impairment of the affected segment of the gut.

Progress on the regulation of DNA methylation in the development of the enteric nervous system / 国际儿科学杂志

The enteric nervous system consists of a network of neurons,neurotransmitters,proteins and its supporting cells in the lining of the gastrointestinal wall. The embryonic development of ENS originates from neural crest stem cells,which start to proliferate and migrate from the neural crest to the mesoderm along the head and tail,and finally migrate into the mesenchyme and form ENS. DNA methylation plays an important role in cell proliferation or differentiation in the process of embryonic development. DNA methylation is regulated by DNA methylation transferase,and the methylation state of the genes is passed on to the offspring in the process of cell proliferation differentiation. DNA methylation is the most profound and extensive mechanism in epigenet-ics research. Thus,this article is to review the recent advances in the effects of epigenetic regulation on the devel-opment of the enteric nervous system.

Experimental study of neural plasticity in chagasic megacolon in rats

This is a cross-sectional and experimental study. The purpose of the study was to measure enteric neurons in rats with chagasic megacolon. Twenty-three male rats inoculated with 1,500,000 trypomastigotes of the Y strain of Trypanosoma cruzi were used. The animals were sedated intramuscularly at zero inoculation time (T0 ) and at sixty days after inoculation (T60), to perform a barium enema test to evaluate the dilatation of the different segments of the colon. Evidence of infection was performed with a blood smear collected from the animals' tails 18 days after inoculation with observation of blood forms. Membrane preparations underwent dual-label immunofluorescence of global and nitrergic neurons with HuC / HuD antibody and nNOS antibody, respectively. Subsequently, quantitative and morphometric analysis of cecal and proximal colon segments were performed. In the quantitative analysis of the proximal colon segment there was a significant decrease in the numbers of total neurons (Hucolo p=0.001), as well as in the number of nitrergic neurons (NOScolo p=0.032) in the population of rats with chagasic megacolon in relation to the control group. In the cecal segment, this difference was not observed in the result of the total neuron counts (Huceco p=0.289) and nitrergic neurons (NOSececo p=0.466). In the morphometric analysis, considering only the cell body area, a significant difference in the size of the neurons with p=0.000 was observed in the cecal segment. The extensive loss of total neurons that cause predominance of nitrergic neurons contributes to the development of megacolon and neuronal volume increase in the cholinergic neurons, this plasticity does not reestablish the lost equilibrium, causing megacolon.

Different inoculum loads of Toxoplasma gondii induce reduction of myenteric neurons of the rat colon / Diferentes inóculos de Toxoplasma gondii induzem a redução de neurônios mioentéricos no cólon de ratos

Abstract Toxoplasmosis, a disease caused by Toxoplasma gondii, is an important health problem, especially in immunocompromised hosts. T. gondii uses the gut wall as an infection gateway, with tropism for muscular and nervous tissues causing intestinal alterations, including some in the enteric nervous system. This study aims at investigating the colon of rats infected by T. gondii in order to understand how the amount of oocysts influences in myenteric neuronal changes. Sixty Wistar rats (Rattus norvegicus) were divided into six groups. One group remained as a control and the others received inocula of 10, 50, 100, 500 or 5,000 oocysts of T. gondii. The animals were euthanized after 30 days of infection. The total neuronal population and the nitrergic subpopulation in the colon myenteric plexus of each animal was counted. The data were statistically analyzed showing less weight gain in rats with 10, 500 and 5,000 oocysts. A decrease in the number of total neurons with 50, 100 or 5,000 oocysts and an increase in the nitrergic population with 10, 100, 500 or 5,000 oocysts were verified. These results show that neuronal alterations are more significant when the infection is induced by larger inocula and reinforces the suspicion that neuronal loss is directed at cholinergic neurons.

Resumo A toxoplasmose, doença causada pelo Toxoplasma gondii, é um importante problema de saúde, principalmente em imunocomprometidos. T. gondii utiliza a parede do intestino como porta de entrada no hospedeiro e tem tropismo pelos tecidos muscular e nervoso provocando alterações intestinais, inclusive no sistema nervoso entérico. Este estudo buscou analisar o cólon de ratos infectados por T. gondii para entender como a quantidade de oocistos influencia nas alterações neuronais mientéricas. Foram utilizados 60 ratos Wistar (Rattus norvegicus) em seis grupos. Um dos grupos permaneceu como controle e os demais receberam inóculos de 10, 50, 100, 500 ou 5.000 oocistos de T. gondii. Os animais foram submetidos a eutanásia após 30 dias de infecção. No plexo mientérico do cólon dos animais foram quantificadas a população neuronal total e a subpopulação nitrérgica. Os dados foram analisados estatisticamente demonstrando inferior ganho de peso nos ratos com 10, 500 e 5.000 oocistos. Verificamos diminuição no número de neurônios totais com inóculos de 50, 100 ou 5.000 oocistos e aumento da população nitrérgica com 10, 100, 500 ou 5000 oocistos. Estes resultados mostram que alterações neuronais são mais significativas quando a infecção é induzida por inóculos maiores e reforça a suspeita de perda neuronal direcionada a neurônios colinérgicos.

Progress of Research on Relationship Between Neuronal Nitric Oxide Synthase and Gastrointestinal Motility Disorders / 胃肠病学

Nitric oxide synthase (NOS) is a key enzyme for production of nitric oxide (NO) in vivo.With the deepening of study on biochemical and molecular characteristics of NOS,the intervention of NOS-NO pathway playing an important role in gastrointestinal motility disorder is appreciated.This article reviewed the progress of research on relationship between neuronal nitric oxide synthase (nNOS) and gastrointestinal motility disorders.

Characteristics and clinical significance of sera anti-enteric neuronal antibodies in patients with irritable bowel syndrome with diarrhea / 基础医学与临床

Objective To detect the sera anti-enteric neuronal antibodies ( AENA ) in irritable bowel syndrome with diarrhea ( IBS-D) patients and analyzed its correlation with IBS-D symptoms to explore the potential roles of AENA in the pathogenesis of IBS.Methods IBS-D patients diagnosed with RomeⅢdiagnostic criteria were en-rolled in this study.The sera of healthy subjects were used as controls.Indirect immunofluorescence ( IIF) was used to detect the sera AENA with the substrate of ileal submucosal plexus of guinea pig .The immune reactivity ( IR) stains were read in blinded method .The bowel symptoms of patients with positive AENA were compared to thatwithnegativeandweeklypositiveantibodies.Results 1)Atotalof127IBS-Dpatientswereenrolledinthis study.The positive rate of sera AENA was 85.8%in IBS-D patients, and 7.0%in healthy controls.Among 109 IBS-D patients with positive IIF reactivity , 23.6%present with strong positive , 43.3% with positive and 18.9%with weakly positive stain .The IR patterns included cytoplasm staining , nucleus staining , cytoplasms and nuclei staining , nuclear membrane staining , cytoplasm and nuclear membrane staining .Six positive sera of healthy control showed cytoplasm staining to substrate neurons .2 ) More patients of IBS-D with positive IR had higher intestinal symptoms scores (>10 scores, 58.8%vs 38.1%), frequent abdominal pain in non-defecation period (91.7%vs 60.0%) , and severe abdominal pain/discomfort before defecation ( 24.7% vs 9.5%) comparing to those with negative and weekly positive IR of AENA;IBS-D patients with positive IR of AENA are more commonly associated with urgency comparing to those with negative IR in IIF (57.1%vs 87.3 ) .Conclusions AENA may play a role in the pathogenesis of IBS , and is a potential biomarker of IBS-D.