{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:09:40Z","timestamp":1760832580441,"version":"build-2065373602"},"reference-count":10,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK103723","R01DK120862"],"award-info":[{"award-number":["R01DK103723","R01DK120862"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The enteric nervous system (ENS) regulates essential gut functions through interactions between neurons and glial cells. While tools for studying neuronal activation are well\u2010established, methods for tracking neuronal inactivation remain underdeveloped. Phosphorylated pyruvate dehydrogenase (pPDH) has emerged as a marker of neuronal inactivity in the brain. This study investigates whether pPDH can similarly serve as a reliable marker of neuronal inactivity in the ENS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole\u2010mount preparations of the colonic myenteric plexus from mice were treated with veratridine (neuronal activator) or tetrodotoxin (neuronal inhibitor). Immunohistochemistry was used to label neurons with HuC\/D and quantify pPDH (inactivity marker) and pERK (activation marker) labelling. Fluorescent signals were analyzed to assess changes in marker expression under different conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TTX treatment increased pPDH labelling, as evidenced by higher fluorescence intensity and a greater percentage of pPDH\u2010positive neurons. In contrast, veratridine reduced pPDH levels, indicating its sensitivity to neuronal activity changes. Together, pPDH and pERK provide reliable measures of neuronal inactivation and activation, respectively, in the ENS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study establishes pPDH as a robust marker for neuronal inactivation in the ENS, complementing existing activation markers like pERK. These findings provide a novel framework for exploring neuron\u2013glia communication and neuronal dynamics in the gut.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.70135","type":"journal-article","created":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T17:59:23Z","timestamp":1755367163000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphorylation of Pyruvate Dehydrogenase as a Marker of Neuronal Inactivity in the Enteric Nervous System"],"prefix":"10.1111","volume":"37","author":[{"given":"Eve","family":"Wemelle","sequence":"first","affiliation":[{"name":"Department of Physiology Michigan State University  East Lansing Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathon L.","family":"McClain","sequence":"additional","affiliation":[{"name":"Department of Physiology Michigan State University  East Lansing Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1145-3227","authenticated-orcid":false,"given":"Brian D.","family":"Gulbransen","sequence":"additional","affiliation":[{"name":"Department of Physiology Michigan State University  East Lansing Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2022"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.5056\/jnm15096"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00049.2017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.12.015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00186.2019"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2018.05.009"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2679"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.64821"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3489\u201017.2018"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12102036"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.70135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T04:04:12Z","timestamp":1760760252000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.70135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,16]]},"references-count":10,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/nmo.70135"],"URL":"https:\/\/doi.org\/10.1111\/nmo.70135","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"type":"print","value":"1350-1925"},{"type":"electronic","value":"1365-2982"}],"subject":[],"published":{"date-parts":[[2025,8,16]]},"assertion":[{"value":"2025-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70135"}}