{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T17:29:19Z","timestamp":1784914159324,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,18]],"date-time":"2021-04-18T00:00:00Z","timestamp":1618704000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Schizophrenia is considered one of the most disabling and severe human diseases worldwide. The etiology of schizophrenia is thought to be multifactorial and evidence suggests that DNA methylation can play an important role in underlying pivotal neurobiological alterations of this disorder. Some studies have demonstrated the effects of dietary supplementation as an alternative approach to the prevention of schizophrenia, including folic acid. However, no study has ever investigated the role of such supplementation in altering the DNA methylation system in the context of schizophrenia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The present study aims to investigate the effects of maternal folic acid supplementation at different doses on nuclear methyltransferase activity of adult rat offspring subjected to an animal model schizophrenia induced by ketamine.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult female Wistar rats, (60\u00a0days old) received folic acid\u2010deficient diet, control diet, or control diet plus folic acid supplementation (at 5, 10, or 50\u00a0mg\/kg) during pregnancy and lactation. After reaching adulthood (60\u00a0days), the male offspring of these dams were subjected to the animal model of schizophrenia induced by 7\u00a0days of ketamine intraperitoneal injection (25\u00a0mg\/kg). After the 7\u2010day protocol, the activity of nuclear methyltransferase was evaluated in the brains of the offspring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maternal folic acid supplementation at 50\u00a0mg\/kg increased methyltransferase activity in the frontal cortex, while 10\u00a0mg\/kg increased methyltransferase activity in the hippocampus. In the striatum of offspring treated with ketamine, maternal deficient diet, control diet, and folic acid supplementation at 5\u00a0mg\/kg decreased methyltransferase activity compared to the control group. The folic acid supplementation at 10 and 50\u00a0mg\/kg reversed this ketamine effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Maternal FA deficiency could be related to schizophrenia pathophysiology, while FA supplementation could present a protective effect since it demonstrated persistent effects in epigenetic parameters in adult offspring.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jdn.10109","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T08:06:14Z","timestamp":1617177974000},"page":"461-467","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Effects of maternal folic acid supplementation on nuclear methyltransferase activity of adult rats subjected to an animal model of schizophrenia"],"prefix":"10.1002","volume":"81","author":[{"given":"Lara","family":"Canever","sequence":"first","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Varela","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo A.","family":"Mastella","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louyse S.","family":"Dam\u00e1zio","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira S.","family":"Valvassori","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o L.","family":"Quevedo","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"},{"name":"Translational Psychiatry Program Department of Psychiatry and Behavioral Sciences McGovern Medical School The University of Texas Health Science Center at Houston (UTHealth)  Houston TX USA"},{"name":"Center of Excellence on Mood Disorders Department of Psychiatry and Behavioral Sciences McGovern Medical School The University of Texas Health Science Center at Houston (UTHealth)  Houston TX USA"},{"name":"Neuroscience Graduate Program The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6658-6444","authenticated-orcid":false,"given":"Alexandra I.","family":"Zugno","sequence":"additional","affiliation":[{"name":"Translational Psychiatry Laboratory Graduate Program in Health Sciences University of Southern Santa Catarina (UNESC)  Crici\u00fama Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,18]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.books.9780890425596"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2005.01202.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2891-13-91"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41437-018-0114-x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2016.00168"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R114.607044"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.06.021"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2018.05.014"},{"issue":"6","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4161\/oxim.3.6.13446","article-title":"A rodent model of schizophrenia reveals increase in creatine kinase activity with associated behavior changes","volume":"3","author":"Canever L.","year":"2010","journal-title":"Oxidative Medicine and Cellular Longevity"},{"issue":"3","key":"e_1_2_10_11_1","first-page":"797","article-title":"Epigenetic regulation of COX\u20102 expression by DNA hypomethylation via NF\u2010\u03baB activation in ketamine\u2010induced ulcerative cystitis","volume":"44","author":"Chuang S. 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