Exploring epigenetic modification of the stress-related FKBP5 gene in mice exposed to alcohol during early postnatal development

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dc.authorscopusidİlknur Dursun / 15126492700
dc.authorwosidİlknur Dursun / AGW-2134-2022
dc.contributor.authorDursun, İlknur
dc.contributor.authorKorkmaz, Nur Damla
dc.contributor.authorFırtına, Sinem
dc.contributor.authorErkoyuncu, Muhammed Salih
dc.contributor.authorAkbaş, Fahri
dc.contributor.authorElibol, Birsen
dc.date.accessioned2025-04-17T13:34:14Z
dc.date.available2025-04-17T13:34:14Z
dc.date.issued2025
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü
dc.description.abstractEarly developmental exposure to alcohol has been implicated in adverse effects on the brain, often associated with the onset of neurodevelopmental disorders. Moreover, maternal alcohol consumption during pregnancy has been linked to the manifestation of mental health disorders, such as depression and anxiety, in subsequent generations. These mood disturbances may be attributed to alterations in protein expressions related to depression and anxiety within the hippocampus. While the precise mechanisms remain elusive, it is likely that pre- and postnatal exposure to alcohol induces changes in hippocampus, potentially through epigenetic modifications. The FKBP5 gene, known to modulate the stress response, is particularly relevant in this context. We postulate that alcohol-induced methylation of the FKBP5 gene disrupts HPA axis function, thereby prompting individuals to anxiety-like and depressive-like behaviors. To investigate this hypothesis, female C57BL/6 pups were subjected to early alcohol exposure via intubation with ethanol mixed in artificial milk from Postnatal Day 3 to Day 20. The intubation control pups were subjected to the same procedures without ethanol or milk, and a nonintubated control group included. Anxiety-like and depressive-like behaviors were assessed using the open field test, plus maze test, forced swim test, and tail suspension test when the pups reached 3 months of age. For epigenetic analysis of the FKBP5 gene, genomic DNA was isolated from hippocampal tissues and subjected to bisulfite conversion to distinguish methylated and unmethylated cytosines. Then, methylation-specific PCR was performed to assess methylation levels. Pups exposed to early postnatal alcohol exhibited increased levels of depression-like behavior and susceptibility to anxiety-like behavior during adolescence, as verified by behavioral assessments. Methylation profiling revealed higher rates of methylation within the stress-associated gene FKBP5 in both the early postnatal alcoholexposed cohort (13.82%) and the intubation control group (3.93%), in contrast to the control cohort devoid of stress or alcohol exposure. These findings suggest a potential epigenetic mechanism underlying the observed behavioral alterations, implicating FKBP5 methylation as a candidate mediator of the increased vulnerability to mood disorders following early postnatal alcohol exposure. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
dc.description.sponsorshipBezmialem Vakıf Üniversitesi Norges Forskningsråd
dc.identifier.citationDursun, I., Korkmaz, N. D., Firtina, S., Erkoyuncu, M. S., Akbas, F., & Elibol, B. (2025). Exploring epigenetic modification of the stress-related FKBP5 gene in mice exposed to alcohol during early postnatal development. Alcohol, 123, 11-17.
dc.identifier.doi10.1016/j.alcohol.2024.09.002
dc.identifier.endpage17
dc.identifier.issn0741-8329
dc.identifier.issn1873-6823
dc.identifier.pmid39245355
dc.identifier.scopus2-s2.0-85215068370
dc.identifier.startpage11
dc.identifier.urihttp://dx.doi.org/10.1016/j.alcohol.2024.09.002
dc.identifier.urihttps://hdl.handle.net/20.500.12713/6274
dc.identifier.volume123
dc.identifier.wosWOS:001402868300001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorDursun, İlknur
dc.institutionauthoridİlknur Dursun / 0000-0001-7094-3336
dc.language.isoen
dc.publisherElsevier inc.
dc.relation.ispartofAlcohol
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAnxiety-Like Behavior
dc.subjectDepression-Like Behavior
dc.subjectEpigenetic
dc.subjectFKBP5 Gene
dc.subjectPostnatal Alcohol Exposure
dc.titleExploring epigenetic modification of the stress-related FKBP5 gene in mice exposed to alcohol during early postnatal development
dc.typeArticle

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