{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T21:47:31Z","timestamp":1774302451140,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF) funded by the Ministry of Education","award":["NRF-2018R1D1A1B07049481 to J.G. Lee"],"award-info":[{"award-number":["NRF-2018R1D1A1B07049481 to J.G. Lee"]}]},{"name":"National Research Foundation of Korea (NRF) funded by the Ministry of Education","award":["NRF- 2020R1I1A3060731 to M.K. Seo \uf1f8"],"award-info":[{"award-number":["NRF- 2020R1I1A3060731 to M.K. Seo \uf1f8"]}]},{"name":"National Research Foundation of Korea (NRF) funded by the Korea government (MIST)","award":["NRF-2020R1A2C1010148 to S.W. Park"],"award-info":[{"award-number":["NRF-2020R1A2C1010148 to S.W. Park"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 17 promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 17 promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 17 promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 17 promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.<\/jats:p>","DOI":"10.3390\/ijms21176331","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T11:53:49Z","timestamp":1598874829000},"page":"6331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3368-4950","authenticated-orcid":false,"given":"Mi Kyoung","family":"Seo","sequence":"first","affiliation":[{"name":"Paik Institute for Clinical Research, Inje University, Busan 47392, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon-gu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan 47392, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dae-Hyun","family":"Seog","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Department of Convergence Biomedical Science, College of Medicine, Dementia and Neurodegenerative Disease Research Center, Inje University, Busan 47392, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Won-Myong","family":"Bahk","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong-Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Haeundae Paik Hospital, Paik Institute for Clinical Research, Inje University, Busan 47392, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Convergence Biomedical Science, College of Medicine, Paik Institute for Clinical Research, Department of Health Science and Technology, Graduate School, Inje University, Busan 47392, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3393-2667","authenticated-orcid":false,"given":"Jung Goo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Paik Institute for Clinical Research, Department of Health Science and Technology, Graduate School, Inje University, Busan 47392, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2307\/1128756","article-title":"Family interaction in abusive, neglectful, and normal families","volume":"49","author":"Burgess","year":"1978","journal-title":"Child Dev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1176\/appi.ajp.158.11.1878","article-title":"Childhood Abuse and Lifetime Psychopathology in a Community Sample","volume":"158","author":"Macmillan","year":"2001","journal-title":"Am. 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