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Recently, it has been demonstrated that epigenetics mechanisms play an important role in this injury and that folic acid (FA) supplementation during pregnancy can affect these epigenetics modifications as well as gene expression. We have identified both positive and negative effects of FA treatment in rats submitted to a model of neonatal hypoxia\u2010ischemia (HI). Considering that FA supplementation is already used in pregnant women and that HI occurs in the peripartum period, this study was designated to evaluate how gestational FA supplementation and neonatal HI affect: apoptosis (caspase\u20103) and expression of synaptic proteins (synapsin and PSD\u201095) and the methylation of histone H3 lysine (K) 4 and 27 in the rat hippocampus. Pregnant Wistar rats were divided according to the diets: standard (SD), supplemented with 2\u00a0mg\/kg of FA or with 20\u00a0mg\/kg of FA. HI procedure was performed at the 7th PND. Protein expression and H3 methylation were evaluated at the 60th PND in the rats\u2019 hippocampus. Neonatal HI increased caspase\u20103 expression decreased synapsin expression and reduced H3K4me2, \u2010me3 and H3K27me2, \u2010me3 in the ipsilateral hippocampus. FA only prevented the augment in caspase\u20103 expression. In conclusion, neonatal HI caused lasting effects on caspase\u20103\u2010mediated cell death (prevented by the FA) and synaptic proteins in the rats\u2019 hippocampus. This is the first study to show that histone modifications may contribute to these pathological findings in the hippocampus of HI animals.<\/jats:p>","DOI":"10.1002\/jdn.10132","type":"journal-article","created":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T11:20:30Z","timestamp":1621682430000},"page":"510-519","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High gestational folic acid supplementation prevents hypoxia\u2010ischemia\u2010induced caspase\u20103 augmenting without changing synapsin and H3 methylation levels in the rat hippocampus"],"prefix":"10.1002","volume":"81","author":[{"given":"Bruna Ferrary","family":"Deniz","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Neuroci\u00eancias Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"},{"name":"Departamento de Ci\u00eancias Morfol\u00f3gicas Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helo\u00edsa Deola","family":"Confortim","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Neuroci\u00eancias Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"},{"name":"Departamento de Ci\u00eancias Morfol\u00f3gicas Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7427-0159","authenticated-orcid":false,"given":"Patr\u00edcia Maidana","family":"Miguel","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Neuroci\u00eancias Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"},{"name":"Departamento de Ci\u00eancias Morfol\u00f3gicas Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loise","family":"Bronauth","sequence":"additional","affiliation":[{"name":"Departamento de Ci\u00eancias Morfol\u00f3gicas Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabela R.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\/Rady Children's Hospital San Diego Department of Cellular &amp; Molecular Medicine Stem Cell Program University of California San Diego School of Medicine  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alysson R.","family":"Muotri","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\/Rady Children's Hospital San Diego Department of Cellular &amp; Molecular Medicine Stem Cell Program University of California San Diego School of Medicine  La Jolla CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-0697","authenticated-orcid":false,"given":"Lenir Orlandi","family":"Pereira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s\u2010Gradua\u00e7\u00e3o em Neuroci\u00eancias Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"},{"name":"Departamento de Ci\u00eancias Morfol\u00f3gicas Universidade Federal do Rio Grande do Sul  Porto Alegre Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,6,13]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"Metabolismo de la metionina en rata gestante: Efectos de la ingesta dietaria de \u00e1cido f\u00f3lico y administracion de valproate","author":"Alonso\u2010Aperte E.","year":"1997"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.10.020"},{"issue":"591","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.neulet.2015.02.029","article-title":"Proteasome regulates transcription\u2010favoring histone methylation, acetylation and ubiquitination in long\u2010term synaptic plasticity","volume":"30","author":"Bach S. 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