D-β-Hydroxybutyrate and lactate mediate the positive effects of exercise on chronic stress by changing the histone modification profile in the hippocampus

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dc.contributor.author Saad, Joelle
dc.date.accessioned 2022-06-15T05:57:46Z
dc.date.available 2022-06-15T05:57:46Z
dc.date.copyright 2021 en_US
dc.date.issued 2021-07-09
dc.identifier.uri http://hdl.handle.net/10725/13664
dc.description.abstract Depression is a very common mental illness and the leading cause of disability worldwide. Some people are more vulnerable than others; however, the underlying mechanisms behind this vulnerability are not well understood. Exercise has long been studied as a lifestyle factor that can be used to counteract the effect of stress. Our objective was to investigate whether two well-established exercise factors, D-β-Hydroxybutyrate and lactate, mediate its positive effects on resilience to chronic stress and social behavior. For that reason, we first blocked the transport of these metabolites to the brain during exercise and assessed whether this blockage abolished the positive effects of exercise on social behavior. Next, we assessed the effects of D-β-Hydroxybutyrate and lactate and determined whether they promote resilience to chronic stress. To that effect, we induced stress in mice using the chronic social defeat stress paradigm. Mice were subjected to chronic social defeat stress while receiving either D-β-Hydroxybutyrate or lactate. Mice that were subjected to chronic social defeat stress exhibited depressive-like behavior, showed increased susceptibility to stress, and displayed increased social avoidance behavior. D-β-Hydroxybutyrate and lactate promoted resilience to stress and rescued social avoidance behavior. The rescue by D-β-Hydroxybutyrate was associated with an increase in histone H3 β-Hydroxybutyrylation levels in the hippocampus. Furthermore, we examined the antidepressant properties of these two exercise factors. To assess that, we subjected the mice to chronic social defeat stress, and then administered our treatments. Both D-β-Hydroxybutyrate and lactate acted as antidepressants when administered after the establishment of a depressive phenotype. Finally, we found that a ketogenic diet known to increase the levels of D-β- Hydroxybutyrate in the brain also mimics the effects of these exercise factors and promotes resilience to stress and rescues social avoidance behavior. The molecular basis behind the rescue effect of D-β-Hydroxybutyrate is still being studied. en_US
dc.language.iso en en_US
dc.subject Gamma-hydroxybutyrate -- Therapeutic use en_US
dc.subject Depression, Mental -- Treatment en_US
dc.subject Antidepressants -- Physiological effect en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.title D-β-Hydroxybutyrate and lactate mediate the positive effects of exercise on chronic stress by changing the histone modification profile in the hippocampus en_US
dc.type Thesis en_US
dc.term.submitted Summer en_US
dc.author.degree Doctor of Pharmacy en_US
dc.author.school SAS en_US
dc.author.idnumber 201603741 en_US
dc.author.commembers Zeeni, Nadine
dc.author.commembers Khalaf, Roy
dc.author.department Natural Sciences en_US
dc.description.physdesc 1 online resource (x, 38 leaves): ill. en_US
dc.author.advisor Sleiman, Sama
dc.keywords Major depressive disorder en_US
dc.keywords depression en_US
dc.keywords voluntary exercise en_US
dc.keywords epigenetic modification en_US
dc.keywords D-β-Hydroxybutyrate en_US
dc.keywords lactate en_US
dc.keywords β-Hydroxybutyrate en_US
dc.keywords lactylation en_US
dc.description.bibliographiccitations Includes bibliographical references (leaf 34-38) en_US
dc.identifier.doi https://doi.org/10.26756/th.2022.248
dc.author.email joelle.saad@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/thesis.php en_US
dc.publisher.institution Lebanese American University en_US
dc.author.affiliation Lebanese American University en_US

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