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DNA methyltransferase 1 (DNMT1) and acid\u2010sensing ion channel 1 (ASIC1) are associated with GHS induced by prenatal maternal stress (PMS). The aim of this study was to investigate the mechanism of DNMT1 mediating the analgesic effect of folic acid (FA) on PMS\u2010induced GHS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>GHS was quantified by electromyogram recordings. The expression of DNMT1, DNMT3a, DNMT3b, and ASIC1 were detected by western blot, RT\u2010PCR, and double\u2010immunofluorescence. Neuronal excitability and proton\u2010elicited currents of dorsal root ganglion (DRG) neurons were determined by whole\u2010cell patch clamp recordings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of DNMT1, but not DNMT3a or DNMT3b, was decreased in DRGs of PMS rats. FA alleviated PMS\u2010induced GHS and hyperexcitability of DRG neurons. FA also increased DNMT1 and decreased ASIC1 expression and sensitivity. Intrathecal injection of DNMT1 inhibitor DC\u2010517 attenuated the effect of FA on GHS alleviation and ASIC1 downregulation. Overexpression of DNMT1 with lentivirus not only rescued ASIC1 upregulation and hypersensitivity, but also alleviated GHS and hyperexcitability of DRG neurons induced by PMS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that increased DNMT1 contributes to the analgesic effect of FA on PMS\u2010induced GHS by reducing ASIC1 expression and sensitivity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14131","type":"journal-article","created":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T07:05:07Z","timestamp":1677999907000},"page":"1678-1689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>DNMT1<\/scp> involved in the analgesic effect of folic acid on gastric hypersensitivity through downregulating <scp>ASIC1<\/scp> in adult offspring rats with prenatal maternal stress"],"prefix":"10.1111","volume":"29","author":[{"given":"Hong\u2010Jun","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou Jiangsu China"},{"name":"Jiangsu Key Laboratory of Anesthesiology &amp; Jiangsu Key Laboratory of Anesthesia and Analgesia Application Technology Xuzhou Medical University  Xuzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu\u2010Chao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University  Suzhou Jiangsu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy W.","family":"Xu","sequence":"additional","affiliation":[{"name":"Suzhou Academy of Xi'an Jiaotong University  Suzhou 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