ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2018
The antioxidant glutathione protects against enteric neuron death in situ, but its depletion is protective during colitis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Elucidating shared genes and pathways in programmed cell death with necrotizing enterocolitis: insights into novel therapeutic targets and glutathione.Translational pediatrics · 2026Article
- Short-chain fatty acids mitigate inflammation and associated metabolic programming of human stem cell-derived enteric glial cells.Journal of neuroinflammation · 2026Article
- Differentiating Enteric Glial Cells Within Intestinal Organoids Derived from Human Pluripotent Stem Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Mechanisms of enteric neuropathy in diverse contexts of gastrointestinal dysfunction.Neurogastroenterology and motility · 2025Review
- The role of the enteric nervous system in the pathogenesis of Clostridioides difficile infection.Nature reviews. Gastroenterology & hepatology · 2025Review
- The role of reactive enteric glia-macrophage interactions in acute and chronic inflammation.Neurogastroenterology and motility · 2025Review
- The Physiology of Enteric Glia.Annual review of physiology · 2025Review
- Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats.Acta histochemica · 2024Article
- Bone marrow-derived mesenchymal stem cells mitigate chronic colitis and enteric neuropathy via anti-inflammatory and anti-oxidative mechanisms.Scientific reports · 2024Article
- Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.Cells · 2024Review
- The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.Biomolecules · 2023Review
- APE1/Ref-1 as a Therapeutic Target for Inflammatory Bowel Disease.Biomolecules · 2023Review
- Stimulator of interferon genes (STING) expression in the enteric nervous system and contributions of glial STING in disease.Neurogastroenterology and motility · 2023Article
- A Comprehensive Analysis of Microflora and Metabolites in the Development of Ulcerative Colitis into Colorectal Cancer Based on the Lung-Gut Correlation Theory.Molecules (Basel, Switzerland) · 2022Article
- Nrf2 attenuates hyperglycemia-induced nNOS impairment in adult mouse primary enteric neuronal crest cells and normalizes stomach function.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Enteric glial biology, intercellular signalling and roles in gastrointestinal disease.Nature reviews. Gastroenterology & hepatology · 2021Review
- Inhibition of APE1/Ref-1 Redox Signaling Alleviates Intestinal Dysfunction and Damage to Myenteric Neurons in a Mouse Model of Spontaneous Chronic Colitis.Inflammatory bowel diseases · 2021Article
- High-fat diet-induced alterations to gut microbiota and gut-derived lipoteichoic acid contributes to the development of enteric neuropathy.Neurogastroenterology and motility · 2020Article
- Enteric neuroplasticity and dysmotility in inflammatory disease: key players and possible therapeutic targets.American journal of physiology. Gastrointestinal and liver physiology · 2019Review
- Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Enteric glia play an important neuroprotective role in the enteric nervous system (ENS) by producing neuroprotective compounds such as the antioxidant reduced glutathione (GSH). The specific cellular pathways that regulate glial production of GSH and how these pathways are altered during, or contribute to, neuroinflammation in situ and in vivo are not fully understood. We investigated this issue using immunohistochemistry to localize GSH synthesis enzymes within the myenteric plexus and tested how the inhibition of GSH synthesis with the selective inhibitor l-buthionine sulfoximine impacts neuronal survival and inflammation. Both enteric glia and neurons express the cellular machinery necessary for GSH synthesis. Furthermore, glial GSH synthesis is necessary for neuronal survival in isolated preparations of myenteric plexus. In vivo depletion of GSH does not induce colitis but alters myenteric plexus neuronal phenotype and survival. Importantly, global depletion of glutathione is protective against some macroscopic and microscopic measures of colonic inflammation. Together, our data highlight the heterogeneous roles of GSH in the myenteric plexus of the ENS and during gastrointestinal inflammation. NEW & NOTEWORTHY Our results show that both enteric glia and neurons express the cellular machinery necessary for glutathione (GSH) synthesis and that glial GSH synthesis is necessary for neuronal survival in isolated enteric nervous system (ENS) preparations. In vivo depletion of GSH with the selective inhibitor l-buthionine sulfoximine is not sufficient to induce inflammation but does alter neuronal neurochemical composition and survival. Together, our data highlight novel heterogeneous roles for GSH in the ENS and during gastrointestinal inflammation.
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