{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:19:50Z","timestamp":1787505590317,"version":"build-2736575974"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":315,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Invitation Research of the Faculty of Medicine","award":["IN62332"],"award-info":[{"award-number":["IN62332"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    . Valproic acid (anticonvulsant medication) has been found to inhibit histone deacetylase activity and suppress hippocampal neurogenesis, which causes memory impairment in both humans and rodents. The neurohormone melatonin, which regulates mammalian seasonal and circadian physiology, has recently been shown to have neuroprotective properties, counteracting memory impairment associated with VPA\u2010caused hippocampal neurogenesis reduction. This study is aimed at investigating the molecular mechanisms of melatonin associated with VPA\u2010induced hippocampal neurogenesis and memory impairment.\n                    <jats:italic>Methods<\/jats:italic>\n                    . Male Spraque\u2010Dawley rats received VPA (300\u2009mg\/kg) twice daily or melatonin (8\u2009mg\/kg\/day) or some rats were given melatonin for 14 days during VPA administration.\n                    <jats:italic>Results<\/jats:italic>\n                    . The VPA\u2010treated rats showed a significant increase in malondialdehyde (MDA) levels in the hippocampus and p21\u2010positive cells in the subgranular zone (SGZ) of the dentate gyrus (DG) but decreased superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) activities. Moreover, VPA significantly decreased levels of nestin, Notchl, nuclear factor erythroid 2\u2010related factor 2 (Nrf2), doublecortin (DCX), sex determining region Y\u2010box 2 (SOX2), and brain\u2010derived neurotrophic factor (BDNF).\n                    <jats:italic>Conclusions<\/jats:italic>\n                    . We found that melatonin was able to counteract these neurotoxic effects, acting as a neuroprotectant in VPA\u2010induced memory hippocampal neurogenesis impairment by preventing intracellular oxidative stress and increasing antioxidant activity.\n                  <\/jats:p>","DOI":"10.1155\/2021\/9997582","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T13:05:08Z","timestamp":1636722308000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Melatonin Ameliorates Valproic Acid\u2010Induced Neurogenesis Impairment: The Role of Oxidative Stress in Adult Rats"],"prefix":"10.1155","volume":"2021","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3226-2713","authenticated-orcid":false,"given":"Anusara","family":"Aranarochana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6929-7709","authenticated-orcid":false,"given":"Apiwat","family":"Sirichoat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanassanun","family":"Pannangrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Wigmore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2872-1542","authenticated-orcid":false,"given":"Jariya Umka","family":"Welbat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03907.x"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(01)00019-3"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms141224438"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2006.03.017"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2011.07.045"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.11.049"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.05.017"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.02.022"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.1999.0603"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfi185"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.08.060"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.24.6969"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2121-9-66"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-05-0480"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.072314"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2002.01873.x"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2006.00407.x"},{"key":"e_1_2_10_18_2","first-page":"609","article-title":"Melatonin reduces oxidative\/nitrosative stress due to drugs, toxins, metals, and herbicides","volume":"29","author":"Reiter R. 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