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The potential benefit of combined versus monotherapy of coenzyme Q10 and fluoxetine on depressive-like behaviors and intermediates coupled to Gsk-3β in rats.

Abstract：

:As a part of the serotoninergic dysfunction implicated in neurobiology of depression, evidence has focused on serotonin (5-HT) receptors downstream signaling intermediates including glycogen synthase kinase-3β (GSK-3β), cAMP response element binding protein (CREB) and brain derived neurotrophic factor (BDNF). Our team previously reported that coenzyme Q10 (CoQ10) exerted antidepressant-like effect in rats exposed to chronic unpredictable mid stress (CUMS) via elevating serotonin levels. However, the effect of CoQ10 has not been elucidated in downstream signaling molecules mediating 5HT receptors' effect involved in depressive disorder hitherto. In the present study, we focused on 5-HT1A and 5-HT2A receptors (activation of 5-HT1A receptor and inhibition of 5-HT2A receptors reduce depressive like-behaviors). We investigated the role of these 5-HT receptors and their linked GSK-3β signaling intermediates as an underlying mechanism of CoQ10 as monotherapy or combined with fluoxetine, a selective serotonin reuptake inhibitor, to alleviate depressive-like phenotype. Effects of CoQ10 (100mg/kg/day) or/and fluoxetine (10mg/kg/day) were determined on 5-HT1A, 5-HT2A receptors mRNA expression, GSK-3β and phosphorylated (p)GSK-3β, CREB, pCREB and BDNF protein expression in rats subjected to CUMS for 6weeks. CUMS rats exhibited obvious depressive-like behaviors (anhedonia-like behavior, negative alterations in social interaction, open field and forced swimming tests) with increased corticosterone and adrenal glands weight, decreased hippocampal levels of pGSK-3β, pCREB and BDNF protein expressions. Additionally, they exhibited decreased hippocampal 5-HT1A and increased 5-HT2A receptor mRNA expression. CoQ10 or fluoxetine significantly attenuated the behavioral and neurochemical alterations in stressed rats with more significance with combined treatment. These findings imply that CoQ10 or/and fluoxetine attenuated CUMS-induced depressive-like behavior partly through modulating dysfunctional regulation of post-serotonergic receptor signaling pathway focusing on GSK-3β, CREB and BDNF.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Abuelezz SA,Hendawy N,Magdy Y

doi

10.1016/j.taap.2017.12.018

subject

Has Abstract

pub_date

2018-02-01 00:00:00

pages

39-48

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(17)30499-4

journal_volume

340

pub_type

杂志文章

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The potential benefit of combined versus monotherapy of coenzyme Q10 and fluoxetine on depressive-like behaviors and intermediates coupled to Gsk-3β in rats.