PMID- 24504086
OWN - NLM
STAT- MEDLINE
DCOM- 20141010
LR  - 20161125
IS  - 1423-0216 (Electronic)
IS  - 1021-7401 (Linking)
VI  - 21
IP  - 4
DP  - 2014
TI  - Akt mediates GSK-3beta phosphorylation in the rat prefrontal cortex during the 
      process of ketamine exerting rapid antidepressant actions.
PG  - 183-8
LID - 10.1159/000356517 [doi]
AB  - Ketamine may produce rapid and sustained antidepressant effects. Despite the fact 
      that the detailed underlying mechanism remains unknown, recent studies have 
      suggested the involvement of the mammalian target of rapamycin (mTOR) pathway and 
      glycogen synthase kinase-3 (GSK-3) signal, respectively, in the process of 
      ketamine exerting antidepressant actions. This study aimed to investigate the 
      mechanism by which ketamine phosphorylates GSK-3beta in the rat prefrontal cortex 
      (PFC) via applying vehicle or the antagonists of mTOR signalling pathway proteins 
      including PI3K/Akt, mTOR and p70S6 kinase to the rats in the forced swimming test 
      (FST) prior to ketamine administration, and subsequently observing the levels of 
      phosphorylated GSK-3beta, mTOR and p70S6K in rat PFC as well as the immobility time 
      of rats in the FST. Our results revealed that compared to treatment with vehicle, 
      ketamine increased the levels of phosphorylated GSK-3beta in rat PFC (p < 0.05), 
      which was attenuated by PI3K/Akt antagonist pretreatment (p < 0.05), but could 
      not be affected by mTOR antagonist or p70S6K antagonist pretreatment. In 
      addition, all the antagonists reversed the ketamine-induced increases in the 
      phosphorylation of mTOR and p70S6K (p < 0.05). They also all abolished the 
      rapid-acting antidepressant actions of ketamine demonstrated by the increased 
      immobility time of rats in the FST. In conclusion, Akt mediates the 
      phosphorylation of GSK-3beta in rat PFC during the process of ketamine exerting 
      rapid antidepressant actions.
FAU - Zhou, Wei
AU  - Zhou W
AD  - Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing 
      University, Nanjing, China.
FAU - Dong, Lin
AU  - Dong L
FAU - Wang, Nan
AU  - Wang N
FAU - Shi, Jin-yun
AU  - Shi JY
FAU - Yang, Jian-jun
AU  - Yang JJ
FAU - Zuo, Zhi-yi
AU  - Zuo ZY
FAU - Zhou, Zhi-qiang
AU  - Zhou ZQ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140206
PL  - Switzerland
TA  - Neuroimmunomodulation
JT  - Neuroimmunomodulation
JID - 9422763
RN  - 0 (Antidepressive Agents)
RN  - 690G0D6V8H (Ketamine)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Blotting, Western
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Phosphorylation
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction/drug effects/physiology
EDAT- 2014/02/08 06:00
MHDA- 2014/10/11 06:00
CRDT- 2014/02/08 06:00
PHST- 2013/01/07 00:00 [received]
PHST- 2013/10/11 00:00 [accepted]
PHST- 2014/02/08 06:00 [entrez]
PHST- 2014/02/08 06:00 [pubmed]
PHST- 2014/10/11 06:00 [medline]
AID - 000356517 [pii]
AID - 10.1159/000356517 [doi]
PST - ppublish
SO  - Neuroimmunomodulation. 2014;21(4):183-8. doi: 10.1159/000356517. Epub 2014 Feb 6.