Lactic acid is a novel antidepressant that mediates its effects by modulating the levels and activity of histone deacetylases (HDAC). (c2018)

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dc.contributor.author Karnib, Nabil H.
dc.date.accessioned 2018-10-01T10:18:13Z
dc.date.available 2018-10-01T10:18:13Z
dc.date.copyright 2018 en_US
dc.date.issued 2018-10-01
dc.date.submitted 2018-02-23
dc.identifier.uri http://hdl.handle.net/10725/8531
dc.description.abstract Depression is one of the most common psychiatric disorders and a leading cause of disability worldwide. Environmental factors, such as chronic stress, can promote depression in some individuals, but have no effect in others. Indeed, susceptible individuals exhibit anxious and anti-social behavior and ultimately develop depression; whereas resilient individuals live normally. These differences in susceptibility versus resilience to stress are thought to be due to distinctive changes in gene expression in the nucleus accumbens and the hippocampal regions of the brain. Here, we use chronic social defeat stress, an ethologically validated model of depression to show that the protein levels of class I histone deacetylases, epigenetic modulators that regulate gene expression, are reduced in susceptible mice and that lactate, an endogenous molecule released after exercise, promotes resilience to stress by restoring their levels. We also assess the anti-depressive effect of lactate. We find that lactate rescues the anti-social and anxiety defects observed in susceptible mice and that this therapeutic effect is mediated by an alternate mechanism. Interestingly, we find that lactate mediates its anti-depressive effect by inhibiting the activity of class II HDACs. Our work reveals that the molecular pathways involved in promoting susceptibility to stress are mediated by a loss of class I HDACs; whereas the molecular mechanisms involved in sustaining the depressive phenotype once susceptibility is established are mediated by induction of HDAC activity. This suggests that HDACs play opposing roles in mediating different aspects of psychiatric diseases and highlights the need to focus on assessing the roles of the specific HDAC isoforms in mediating this disorder. en_US
dc.language.iso en en_US
dc.subject Lebanese American University -- Dissertations en_US
dc.subject Dissertations, Academic en_US
dc.subject Histone Deacetylase Inhibitors en_US
dc.subject Lactic acid en_US
dc.subject Antidepressants en_US
dc.title Lactic acid is a novel antidepressant that mediates its effects by modulating the levels and activity of histone deacetylases (HDAC). (c2018) en_US
dc.type Thesis en_US
dc.term.submitted Spring en_US
dc.author.degree MS in Molecular Biology en_US
dc.author.school SAS en_US
dc.author.idnumber 201201103 en_US
dc.author.commembers Khalaf, Roy
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: ix, 47 leaves; 30 cm. available at RNL. en_US
dc.author.advisor Sleiman, Sama F.
dc.keywords Chronic Social Defeat Stress en_US
dc.keywords Resilience en_US
dc.keywords Antidepressant en_US
dc.keywords Class I HDACs en_US
dc.description.bibliographiccitations Bibliography : leaves 41-47. en_US
dc.identifier.doi https://doi.org/10.26756/th.2018.64 en_US
dc.author.email nabil.karnib@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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