Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/163083
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dc.contributor.authorSelvaraji, Sharmeleeen_US
dc.contributor.authorEfthymios, Motakisen_US
dc.contributor.authorFoo, Roger Sik Yinen_US
dc.contributor.authorFann, David Y.en_US
dc.contributor.authorLai, Mitchell Kim Pengen_US
dc.contributor.authorChen, Christopher Li Hsianen_US
dc.contributor.authorLim, Kah-Leongen_US
dc.contributor.authorArumugam, Thiruma V.en_US
dc.date.accessioned2022-11-21T02:53:40Z-
dc.date.available2022-11-21T02:53:40Z-
dc.date.issued2022-
dc.identifier.citationSelvaraji, S., Efthymios, M., Foo, R. S. Y., Fann, D. Y., Lai, M. K. P., Chen, C. L. H., Lim, K. & Arumugam, T. V. (2022). Time-restricted feeding modulates the DNA methylation landscape, attenuates hallmark neuropathology and cognitive impairment in a mouse model of vascular dementia. Theranostics, 12(7), 3007-3023. https://dx.doi.org/10.7150/thno.71815en_US
dc.identifier.issn1838-7640en_US
dc.identifier.urihttps://hdl.handle.net/10356/163083-
dc.description.abstractObjective: Vascular dementia (VaD) is the second most common cause of dementia worldwide. The increasing contribution of lifestyle-associated risk factors to VaD has pointed towards gene-environment interactions (i.e. epigenetics). This study thus aims to investigate the DNA methylation landscape in a chronic cerebral hypoperfusion (CCH) mouse model of VaD. As a nexus between the gene-environment interaction, intermittent fasting (IF) was introduced as a prophylactic intervention. Methods: Bilateral common carotid artery stenosis (BCAS) was used to induce CCH by placing micro-coils of 0.18 mm in each common carotid artery of the mice. The coils were left in the mice for 7, 15 and 30 days to study temporal differences. IF was introduced for 16 h daily for 4 months prior to BCAS. Reduced Representation Bisulfite Sequencing (RRBS) was used to study the DNA methylation landscape. Cognitive impairment was measured using Barnes Maze Test. White matter lesions (WML) and neuronal loss were measured using Luxol fast blue staining and cresyl violet staining respectively. Results: IF mice subjected to CCH displayed significantly better cognitive learning ability and memory, improved neuropathological alterations with reduced WMLs and neuronal loss. Modulation of DNA methylation patterns in the cortex of AL CCH mice was re-modelled and signs of reversal was observed in IF CCH mice across all three timepoints. Conclusions: These findings provide an understanding of how IF may protect the brain against damage caused by CCH and show promise in offering potential beneficial effects in mitigating the neuropathology and cognitive deficits in VaD.en_US
dc.description.sponsorshipMinistry of Education (MOE)en_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.language.isoenen_US
dc.relationNMRC-CBRG-0102/2016en_US
dc.relationNMRC/CSA-SI/007/2016en_US
dc.relationNMRC/OFIRG/ 0036/2017en_US
dc.relationMOE2017-T3-1-002en_US
dc.relation.ispartofTheranosticsen_US
dc.rights© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.en_US
dc.subjectScience::Medicineen_US
dc.titleTime-restricted feeding modulates the DNA methylation landscape, attenuates hallmark neuropathology and cognitive impairment in a mouse model of vascular dementiaen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.identifier.doi10.7150/thno.71815-
dc.description.versionPublished versionen_US
dc.identifier.pmid35547760-
dc.identifier.scopus2-s2.0-85128592658-
dc.identifier.issue7en_US
dc.identifier.volume12en_US
dc.identifier.spage3007en_US
dc.identifier.epage3023en_US
dc.subject.keywordsIntermittent Fastingen_US
dc.subject.keywordsDNA Methylationen_US
dc.description.acknowledgementThis work was supported by the National Medical Research Council Research Grants (NMRC-CBRG-0102/2016; NMRC/CSA-SI/007/2016 and NMRC/OFIRG/ 0036/2017), Singapore and the Ministry of Education (MOE2017-T3-1-002), Singapore and La Trobe University, Australia.en_US
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