PMID- 29291430
OWN - NLM
STAT- MEDLINE
DCOM- 20180724
LR  - 20221207
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 340
DP  - 2018 Feb 1
TI  - The potential benefit of combined versus monotherapy of coenzyme Q10 and 
      fluoxetine on depressive-like behaviors and intermediates coupled to Gsk-3beta in 
      rats.
PG  - 39-48
LID - S0041-008X(17)30499-4 [pii]
LID - 10.1016/j.taap.2017.12.018 [doi]
AB  - 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-3beta (GSK-3beta), 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-HT(1A) and 5-HT(2A) receptors (activation of 5-HT(1A) receptor and inhibition 
      of 5-HT(2A) receptors reduce depressive like-behaviors). We investigated the role 
      of these 5-HT receptors and their linked GSK-3beta 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-HT(1A), 5-HT(2A) receptors mRNA expression, GSK-3beta and phosphorylated 
      (p)GSK-3beta, 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-3beta, pCREB and BDNF protein expressions. 
      Additionally, they exhibited decreased hippocampal 5-HT(1A) and increased 
      5-HT(2A) 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-3beta, CREB and BDNF.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Abuelezz, Sally A
AU  - Abuelezz SA
AD  - Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
FAU - Hendawy, Nevien
AU  - Hendawy N
AD  - Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt. 
      Electronic address: drnevien_hendawi@med.asu.edu.eg.
FAU - Magdy, Yosra
AU  - Magdy Y
AD  - Pharmacology Department, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
DEP - 20171229
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antidepressive Agents)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 1339-63-5 (Ubiquinone)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EJ27X76M46 (coenzyme Q10)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*administration & dosage
MH  - Depressive Disorder/drug therapy/*enzymology/*psychology
MH  - Drug Therapy, Combination
MH  - Fluoxetine/*administration & dosage
MH  - Glycogen Synthase Kinase 3 beta/antagonists & inhibitors/*metabolism
MH  - Random Allocation
MH  - Rats
MH  - Rats, Wistar
MH  - Selective Serotonin Reuptake Inhibitors/administration & dosage
MH  - Ubiquinone/administration & dosage/*analogs & derivatives
OTO - NOTNLM
OT  - Brain derived neurotrophic factor
OT  - Co-enzyme Q10
OT  - Depressive-like behavior
OT  - Fluoxetine
OT  - Glycogen synthase kinase-3beta
OT  - cAMP response element binding protein
EDAT- 2018/01/02 06:00
MHDA- 2018/07/25 06:00
CRDT- 2018/01/02 06:00
PHST- 2017/08/26 00:00 [received]
PHST- 2017/12/25 00:00 [revised]
PHST- 2017/12/28 00:00 [accepted]
PHST- 2018/01/02 06:00 [pubmed]
PHST- 2018/07/25 06:00 [medline]
PHST- 2018/01/02 06:00 [entrez]
AID - S0041-008X(17)30499-4 [pii]
AID - 10.1016/j.taap.2017.12.018 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2018 Feb 1;340:39-48. doi: 10.1016/j.taap.2017.12.018. 
      Epub 2017 Dec 29.