Abstract：
:Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fluoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fluoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants.
journal_name
Psychoneuroendocrinologyjournal_title
Psychoneuroendocrinologyauthors
Adzic M,Lukic I,Mitic M,Djordjevic J,Elaković I,Djordjevic A,Krstic-Demonacos M,Matić G,Radojcic Mdoi
10.1016/j.psyneuen.2013.07.019subject
Has Abstractpub_date
2013-12-01 00:00:00pages
2914-24issue
12eissn
0306-4530issn
1873-3360pii
S0306-4530(13)00269-2journal_volume
38pub_type
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journal_title：Psychoneuroendocrinology
pub_type： 临床试验,杂志文章,随机对照试验
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pub_type： 杂志文章,随机对照试验
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