Enteric Nervous System: Neuropathic Gastrointestinal Motility

Wood, Jackie D.

doi:10.1007/s10620-016-4183-5

Cited by 27 publications

(26 citation statements)

References 85 publications

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“…The small intestine ENS is equipped to perform functions relating to inflammation, digestion, secretion and motility among others [67][68][69]. The identification of several neuronal terms for central genes in the small intestine network is in line with such literature findings ( Figs 10 and 11) [67][68][69].…”

Section: Randomization Experimentssupporting

confidence: 78%

“…These vitamins are essential for several biological processes and their enrichment in large intestine specific gene network only seems natural (Figs 10 and 11). The brain-in-the-gut or the enteric nervous system (ENS) is the largest component of the autonomous nervous system [67][68][69]. The small intestine ENS is equipped to perform functions relating to inflammation, digestion, secretion and motility among others [67][68][69].…”

Section: Randomization Experimentsmentioning

confidence: 99%

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Tissue-specific mouse mRNA isoform networks

Kandoi

Dickerson

2019

Preprint

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Alternative Splicing produces multiple mRNA isoforms of genes which have important diverse roles such as regulation of gene expression, human heritable diseases, and response to environmental stresses. However, little has been done to assign functions at the mRNA isoform level. Functional networks, where the interactions are quantified by their probability of being involved in the same biological process are typically generated at the gene level. We use a diverse array of tissue-specific RNA-seq datasets and sequence information to train random forest models that predict the functional networks. Since there is no mRNA isoform-level gold standard, we use single isoform genes co-annotated to Gene Ontology biological process annotations, Kyoto Encyclopedia of Genes and Genomes pathways, BioCyc pathways and protein-protein interactions as functionally related (positive pair). To generate the non-functional pairs (negative pair), we use the Gene Ontology annotations tagged with "NOT" qualifier. We describe 17 Tissue-spEcific mrNa iSoform functIOnal Networks (TENSION) following a leave-one-tissue-out strategy in addition to an organism level reference functional network for mouse. We validate our predictions by comparing its performance with previous methods, randomized positive and negative class labels, updated Gene Ontology annotations, and by literature evidence. We demonstrate the ability of our networks to reveal tissue-specific functional differences of the isoforms of the same genes.

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Section: Randomization Experimentssupporting

confidence: 78%

Section: Randomization Experimentsmentioning

confidence: 99%

Tissue-specific mouse mRNA isoform networks

Kandoi

Dickerson

2019

Preprint

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“… 2 Broad abnormalities in the brain–gut axis contribute to the pain component of FGIDs, 3 but it is clear that changes in gut motility are driven primarily by alterations to the enteric nervous system (ENS). 4 The ENS is a complex network of enteric neurons and glia embedded within the gut wall that provides local control over reflexive gut functions such as fluid exchange across the mucosa, local blood flow, and patterns of motility. 5 Inflammation can disrupt the control of these gastrointestinal (GI) reflexes by altering both the function and survival of enteric neurons that then contribute to the development of FGIDs.…”

mentioning

confidence: 99%

Communication Between Enteric Neurons, Glia, and Nociceptors Underlies the Effects of Tachykinins on Neuroinflammation

Delvalle

Dharshika

Morales‐Soto

et al. 2018

Cellular and Molecular Gastroenterology and Hepatology

119

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Background & AimsTachykinins are involved in physiological and pathophysiological mechanisms in the gastrointestinal tract. The major sources of tachykinins in the gut are intrinsic enteric neurons in the enteric nervous system and extrinsic nerve fibers from the dorsal root and vagal ganglia. Although tachykinins are important mediators in the enteric nervous system, how they contribute to neuroinflammation through effects on neurons and glia is not fully understood. Here, we tested the hypothesis that tachykinins contribute to enteric neuroinflammation through mechanisms that involve intercellular neuron-glia signaling.MethodsWe used immunohistochemistry and quantitative real-time polymerase chain reaction, and studied cellular activity using transient-receptor potential vanilloid-1 (TRPV1)tm1(cre)Bbm/J::Polr2atm1(CAG-GCaMP5g,-tdTomato)Tvrd and Sox10CreERT2::Polr2atm1(CAG-GCaMP5g,-tdTomato)Tvrd mice or Fluo-4. We used the 2,4-di-nitrobenzene sulfonic acid (DNBS) model of colitis to study neuroinflammation, glial reactivity, and neurogenic contractility. We used Sox10::CreERT2+/-/Rpl22tm1.1Psam/J mice to selectively study glial transcriptional changes.ResultsTachykinins are expressed predominantly by intrinsic neuronal varicosities whereas neurokinin-2 receptors (NK2Rs) are expressed predominantly by enteric neurons and TRPV1-positive neuronal varicosities. Stimulation of NK2Rs drives responses in neuronal varicosities that are propagated to enteric glia and neurons. Antagonizing NK2R signaling enhanced recovery from colitis and prevented the development of reactive gliosis, neuroinflammation, and enhanced neuronal contractions. Inflammation drove changes in enteric glial gene expression and function, and antagonizing NK2R signaling mitigated these changes. Neurokinin A–induced neurodegeneration requires glial connexin-43 hemichannel activity.ConclusionsOur results show that tachykinins drive enteric neuroinflammation through a multicellular cascade involving enteric neurons, TRPV1-positive neuronal varicosities, and enteric glia. Therapies targeting components of this pathway could broadly benefit the treatment of dysmotility and pain after acute inflammation in the intestine.

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“…Nervous and humoral factors, more precisely neurotransmitters of the enteric nervous system, regulate the spontaneous rhythmic contraction and relaxation of smooth muscles of the intestine. The enteric nervous system (brain-in-the-gut) is essential for normal motility of the small intestine [21]. It is known that extracts which affect the contractility of the intestine, have neurophysiological activity [22,23].…”

Section: Discussionmentioning

confidence: 99%

Antispasmodic Effect of Blackcurrant (<b><i>Ribes nigrum</i></b> L.) Juice and Its Potential Use as Functional Food in Gastrointestinal Disorders

et al. 2018

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Objective: The purpose of this study was to investigate the relaxative effects of blackcurrant juice on the gastrointestinal smooth muscle in vitro. Materials and Methods: Berries of the blackcurrant cultivar Ometa were used for the preparation of the juice used. The spasmolytic activity of blackcurrant juice was tested on rat ileum isolated from male Wistar rats by monitoring its influence on spontaneous contractions, as well as contractions induced by potassium chloride (KCl), barium chloride (BaCl₂), calcium chloride (CaCl₂), and acetylcholine (Ach). The results are expressed as the mean ± standard deviation obtained in 6 measurements and statistical significance was determined by the Student t test, with p < 0.05 taken as significant. Results: The blackcurrant cultivar Ometa significantly reduced the frequency and the amplitude of spontaneous contractions (57.94 ± 3.44%) and Ach-induced contractions (42.74 ± 5.36%; p < 0.05) of the isolated rat ileum. Cumulative concentrations (0.01–3 mg/mL) of the Ometa juice also reduced contractions of the isolated rat ileum stimulated by KCl (51.46 ± 6.87%), CaCl₂ (57.54 ± 6.47%), and BaCl₂ (58.54 ± 10.55%). The inhibitory effects of the juice were proportional to the applied concentration. Conclusion: The antispasmodic effect of Ometa cultivar shows that common gastrointestinal disorders could be treated by the functional food.

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Enteric Nervous System: Neuropathic Gastrointestinal Motility

Cited by 27 publications

References 85 publications

Tissue-specific mouse mRNA isoform networks

Tissue-specific mouse mRNA isoform networks

Communication Between Enteric Neurons, Glia, and Nociceptors Underlies the Effects of Tachykinins on Neuroinflammation

Antispasmodic Effect of Blackcurrant (<b><i>Ribes nigrum</i></b> L.) Juice and Its Potential Use as Functional Food in Gastrointestinal Disorders

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