{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T04:02:42Z","timestamp":1768536162259,"version":"3.49.0"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T00:00:00Z","timestamp":1680480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2020R1A2C1009499"],"award-info":[{"award-number":["2020R1A2C1009499"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["KK2352-10"],"award-info":[{"award-number":["KK2352-10"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003704","name":"Korea Research Institute of Chemical Technology","doi-asserted-by":"publisher","award":["2020R1A2C1009499"],"award-info":[{"award-number":["2020R1A2C1009499"]}],"id":[{"id":"10.13039\/501100003704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003704","name":"Korea Research Institute of Chemical Technology","doi-asserted-by":"publisher","award":["KK2352-10"],"award-info":[{"award-number":["KK2352-10"]}],"id":[{"id":"10.13039\/501100003704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity. VPA affects neurotransmission and gene expression through epigenetic mechanisms by acting as a histone deacetylase inhibitor and has been used to establish animal models of autism spectrum disorder (ASD). However, studies on the long-term effects of early exposure to VPA on glucocorticoid and neurosteroid synthesis in the brain are lacking. Therefore, this study aimed to investigate the long-term changes in metabolic alterations and gene expression regulation according to sex, using metabolic steroid profiling data from cerebral cortex samples of rats four weeks after VPA exposure (400 mg\/kg). In neonatal VPA-exposed models, estradiol levels decreased, and cytochrome P450 19A1 gene (Cyp19a1) expression was reduced in the prepubertal male cortex. Progesterone and allopregnanolone levels decreased, and 3\u03b2-hydroxysteroid dehydrogenase 1 gene (Hsd3b1) expression was also downregulated in the prepubertal female cortex. Furthermore, cortisol levels increased, and mRNA expression of the nuclear receptor subfamily 3 group C member 1 gene (Nr3c1) was downregulated in the cortices of both sexes. Unlike the neonatal VPA-exposed models, although a decrease in progestin and estradiol levels was observed in females and males, respectively, no differences were observed in cortisol levels in the cortex tissues of 8-week-old adult rats administered VPA for four weeks. These results indicate that early environmental chemical exposure induces long-term neurosteroid metabolic effects in the brain, with differences according to sex.<\/jats:p>","DOI":"10.3390\/ijms24076681","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T02:30:15Z","timestamp":1680575415000},"page":"6681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats"],"prefix":"10.3390","volume":"24","author":[{"given":"Soon-Ae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Hye","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Eulji University, Daejeon 34824, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jangjae","family":"Lee","sequence":"additional","affiliation":[{"name":"Chemical Analysis Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of Korea"},{"name":"Department of Chemistry, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9605-5086","authenticated-orcid":false,"given":"Sung-Hee","family":"Cho","sequence":"additional","affiliation":[{"name":"Chemical Analysis Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Exp. 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