Long-Term Epigenetic Regulation of Foxo3 Expression in Neonatal Valproate-Exposed Rat Hippocampus with Sex-Related Differences.
| Title: | Long-Term Epigenetic Regulation of Foxo3 Expression in Neonatal Valproate-Exposed Rat Hippocampus with Sex-Related Differences. |
|---|---|
| Authors: | Jang, Eun-Hye1 (AUTHOR) dmter12@gmail.com, Kim, Soon-Ae1 (AUTHOR) sakim@eulji.ac.kr |
| Source: | International Journal of Molecular Sciences. May2024, Vol. 25 Issue 10, p5287. 13p. |
| Subject Terms: | *GENE expression, *EPIGENETICS, *AUTISM spectrum disorders, *VALPROIC acid, *HIPPOCAMPUS (Brain), *ANIMAL social behavior |
| Abstract: | Perinatal exposure to valproic acid is commonly used for autism spectrum disorder (ASD) animal model development. The inhibition of histone deacetylases by VPA has been proposed to induce epigenetic changes during neurodevelopment, but the specific alterations in genetic expression underlying ASD-like behavioral changes remain unclear. We used qPCR-based gene expression and epigenetics tools and Western blotting in the hippocampi of neonatal valproic acid-exposed animals at 4 weeks of age and conducted the social interaction test to detect behavioral changes. Significant alterations in gene expression were observed in males, particularly concerning mRNA expression of Foxo3, which was significantly associated with behavioral changes. Moreover, notable differences were observed in H3K27ac chromatin immunoprecipitation, quantitative PCR (ChIP-qPCR), and methylation-sensitive restriction enzyme-based qPCR targeting the Foxo3 gene promoter region. These findings provide evidence that epigenetically regulated hippocampal Foxo3 expression may influence social interaction-related behavioral changes. Furthermore, identifying sex-specific gene expression and epigenetic changes in this model may elucidate the sex disparity observed in autism spectrum disorder prevalence. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: Long-Term Epigenetic Regulation of Foxo3 Expression in Neonatal Valproate-Exposed Rat Hippocampus with Sex-Related Differences. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Jang%2C+Eun-Hye%22">Jang, Eun-Hye</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> dmter12@gmail.com</i><br /><searchLink fieldCode="AR" term="%22Kim%2C+Soon-Ae%22">Kim, Soon-Ae</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> sakim@eulji.ac.kr</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Molecular+Sciences%22">International Journal of Molecular Sciences</searchLink>. May2024, Vol. 25 Issue 10, p5287. 13p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22GENE+expression%22">GENE expression</searchLink><br />*<searchLink fieldCode="DE" term="%22EPIGENETICS%22">EPIGENETICS</searchLink><br />*<searchLink fieldCode="DE" term="%22AUTISM+spectrum+disorders%22">AUTISM spectrum disorders</searchLink><br />*<searchLink fieldCode="DE" term="%22VALPROIC+acid%22">VALPROIC acid</searchLink><br />*<searchLink fieldCode="DE" term="%22HIPPOCAMPUS+%28Brain%29%22">HIPPOCAMPUS (Brain)</searchLink><br />*<searchLink fieldCode="DE" term="%22ANIMAL+social+behavior%22">ANIMAL social behavior</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Perinatal exposure to valproic acid is commonly used for autism spectrum disorder (ASD) animal model development. The inhibition of histone deacetylases by VPA has been proposed to induce epigenetic changes during neurodevelopment, but the specific alterations in genetic expression underlying ASD-like behavioral changes remain unclear. We used qPCR-based gene expression and epigenetics tools and Western blotting in the hippocampi of neonatal valproic acid-exposed animals at 4 weeks of age and conducted the social interaction test to detect behavioral changes. Significant alterations in gene expression were observed in males, particularly concerning mRNA expression of Foxo3, which was significantly associated with behavioral changes. Moreover, notable differences were observed in H3K27ac chromatin immunoprecipitation, quantitative PCR (ChIP-qPCR), and methylation-sensitive restriction enzyme-based qPCR targeting the Foxo3 gene promoter region. These findings provide evidence that epigenetically regulated hippocampal Foxo3 expression may influence social interaction-related behavioral changes. Furthermore, identifying sex-specific gene expression and epigenetic changes in this model may elucidate the sex disparity observed in autism spectrum disorder prevalence. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/ijms25105287 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 5287 Subjects: – SubjectFull: GENE expression Type: general – SubjectFull: EPIGENETICS Type: general – SubjectFull: AUTISM spectrum disorders Type: general – SubjectFull: VALPROIC acid Type: general – SubjectFull: HIPPOCAMPUS (Brain) Type: general – SubjectFull: ANIMAL social behavior Type: general Titles: – TitleFull: Long-Term Epigenetic Regulation of Foxo3 Expression in Neonatal Valproate-Exposed Rat Hippocampus with Sex-Related Differences. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Jang, Eun-Hye – PersonEntity: Name: NameFull: Kim, Soon-Ae IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 05 Text: May2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 16616596 Numbering: – Type: volume Value: 25 – Type: issue Value: 10 Titles: – TitleFull: International Journal of Molecular Sciences Type: main |
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