Methionine mediates resilience to chronic social defeat by modulating NMDA receptor expression in the cortex. (c2018)

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dc.contributor.author Bilen, Maria
dc.date.accessioned 2018-10-17T06:03:29Z
dc.date.available 2018-10-17T06:03:29Z
dc.date.copyright 2018 en_US
dc.date.issued 2018-10-17
dc.date.submitted 2018-07-23
dc.identifier.uri http://hdl.handle.net/10725/8647
dc.description.abstract Nowadays, Major Depressive Disorder (MDD) has become a leading cause of disability in the world. Most patients suffering from depression are treated with serotonin reuptake inhibitors, but resistance has started emerging. Therefore, alternative treatments should be considered. Recent studies have shown that the brains of individuals affected with neuropsychiatric disorders have disrupted methylation patterns. Since methionine is the precursor of S-adenosylmethionine (SAM), a cofactor for most methyltransferases, the aim of the study was to examine the effect of methionine supplementation on chronic social defeat (CSD), the animal model of depression. Male C57BL/6 mice were subjected to CSD for 10 consecutive days, followed by behavioral testing to assess anxiety and depression-like symptoms. Animals subjected to CSD and treated with 1.55mg/Kg of methionine through intraperitoneal injections, showed a rescue in the social avoidance behavior. Molecular analysis of the cortices of these animals revealed that methionine treatment restored the expression levels of NMDA receptor subunits, Grin 1, Grin 2a and Grin 2b to baseline when compared to the increased levels observed in defeated animals treated with saline only. This increase was accompanied by a reduction in the protein levels of the histone methyltransferase known to modulate NMDA receptor expression, SetDB1 in defeated animals, while methionine injections returned SetDB1 levels to baseline. These findings suggest that methionine supplementation could serve as an antidepressant due to its role in modifying the histone methylation patterns and possibly regulating the NMDA gene expression. en_US
dc.language.iso en en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.subject Methyl aspartate en_US
dc.subject Methionine -- Therapeutic use en_US
dc.subject Depression, Mental -- Animal models en_US
dc.subject Antidepressants en_US
dc.title Methionine mediates resilience to chronic social defeat by modulating NMDA receptor expression in the cortex. (c2018) en_US
dc.type Thesis en_US
dc.term.submitted Summer en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 201301802 en_US
dc.author.commembers Tokajian, Sima
dc.author.commembers Stephan, Joseph
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.description.physdesc 1 hard copy: x, 45 leaves; ill.; 30 cm. available at RNL. en_US
dc.author.advisor Sleiman, Sama
dc.keywords Methionine en_US
dc.keywords Major Depressive disorder en_US
dc.keywords Chronic social defeat en_US
dc.keywords Cortex en_US
dc.keywords NMDA receptor en_US
dc.keywords SETDB1 en_US
dc.keywords H3K9me3 en_US
dc.keywords SAM en_US
dc.description.bibliographiccitations Bibliography : leaves 39-45. en_US
dc.identifier.doi https://doi.org/10.26756/th.2018.98 en_US
dc.author.email maria.bilen@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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