{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T21:29:29Z","timestamp":1775597369679,"version":"3.50.1"},"reference-count":66,"publisher":"IMR Press","issue":"7","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Application Development of Standardized Herbal Resources from the Korea Institute of Oriental Medicine","award":["KSN1822320"],"award-info":[{"award-number":["KSN1822320"]}]},{"name":"Regional Innovation Strategy through the National Research Foundation of Korea funded by the Ministry of Education","award":["2021RIS-002"],"award-info":[{"award-number":["2021RIS-002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Background: DNA methylation forms 5-methylcytosine and its regulation in the hippocampus is critical for learning and memory. Indeed, dysregulation of DNA methylation is associated with neurological diseases. Alzheimer\u2019s disease (AD) is the predominant of dementia and a neurodegenerative disorder. Methods: We examined the learning and memory function in 3- and 9-month-old wild-type and 5xfamiliar Alzheimer\u2019s disease (5xFAD) transgenic mice by performing the object recognition memory and Y-maze tests, and identified the hippocampal amyloid beta burden. To investigate the epigenetically regulated genes involved in the development or neuropathology of AD, we performed genome-wide DNA methylation sequencing and RNA sequencing analyses in the hippocampus of 9-month-old wild-type and 5xFAD tg mice. To validate the genes inversely regulated by epigenetics, we confirmed their methylation status and mRNA levels. Results: At 9 months of age, 5xFAD tg mice showed significant cognitive impairment and amyloid-beta plaques in the hippocampus. DNA methylation sequencing identified a total of 13,777 differentially methylated regions, including 4484 of hyper- and 9293 of hypomethylated regions, that are associated with several gene ontology (GO) terms including \u2018nervous system development\u2019 and \u2018axon guidance\u2019. In RNA sequencing analysis, we confirmed a total of 101 differentially expressed genes, including 52 up- and 49 downregulated genes, associated with GO functions such as \u2018positive regulation of synaptic transmission, glutamatergic\u2019 and \u2018actin filament organization\u2019. Through further integrated analysis of DNA methylation and RNA sequencing, three epigenetically regulated genes were selected: thymus cell antigen 1, theta (Thy1), myosin VI (Myo6), and filamin A-interacting protein 1-like (Filip1l). The methylation level of Thy1 decreased and its mRNA levels increased, whereas that of Myo6 and Filip1l increased and their mRNA levels decreased. The common functions of these three genes may be associated with the neural cytoskeleton and synaptic plasticity. Conclusions: We suggest that the candidate genes epigenetically play a role in AD-associated neuropathology (i.e., amyloid-beta plaques) and memory deficit by influencing neural structure and synaptic plasticity. Furthermore, counteracting dysregulated epigenetic changes may delay or ameliorate AD onset or symptoms.<\/jats:p>","DOI":"10.31083\/j.jin2307138","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T09:33:16Z","timestamp":1721986396000},"source":"Crossref","is-referenced-by-count":4,"title":["Integrated Genome-Wide Analysis of DNA Methylation and Gene Expression in the Hippocampi of 5xFAD Alzheimer\u2019s Disease Mouse Model"],"prefix":"10.31083","volume":"23","author":[{"given":"Sueun","family":"Lee","sequence":"first","affiliation":[{"name":"Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 58245 Naju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hae-June","family":"Lee","sequence":"first","affiliation":[{"name":"Division of Radiation Biomedical Research, Korea Institute of Radiological & Medical Sciences, 01812 Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Mi","family":"Chun","sequence":"first","affiliation":[{"name":"Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 58245 Naju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bokyung","family":"Jung","sequence":"first","affiliation":[{"name":"Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaebum","family":"Kim","sequence":"first","affiliation":[{"name":"Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changjong","family":"Moon","sequence":"first","affiliation":[{"name":"Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul","family":"Kim","sequence":"first","affiliation":[{"name":"KM Data Division, Korea Institute of Oriental Medicine, 34054 Daejeon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joong-Sun","family":"Kim","sequence":"first","affiliation":[{"name":"Departments of Veterinary Anatomy and Animal Behavior, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, 61186 Gwangju, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"16242","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Jin B, Li Y, Robertson KD. 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