PMID- 26522512
OWN - NLM
STAT- MEDLINE
DCOM- 20160913
LR  - 20211203
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Nov 2
TI  - Fluoxetine regulates mTOR signalling in a region-dependent manner in 
      depression-like mice.
PG  - 16024
LID - 10.1038/srep16024 [doi]
LID - 16024
AB  - Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) 
      signaling pathway has an important role in ketamine-induced, rapid antidepressant 
      effects despite the acute administration of fluoxetine not affecting mTOR 
      phosphorylation in the brain. However, the effects of long-term fluoxetine 
      treatment on mTOR modulation have not been assessed to date. In the present 
      study, we examined whether fluoxetine, a type of commonly used antidepressant 
      agent, alters mTOR signaling following chronic administration in different brain 
      regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We 
      also investigated whether fluoxetine enhanced synaptic protein levels in these 
      regions via the activation of the mTOR signaling pathway and its downstream 
      regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine 
      treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR 
      phosphorylation reduction in the hippocampus and amygdala of mice but not in the 
      frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and 
      synapsin I levels were reversed by fluoxetine, and these effects were blocked by 
      rapamycin only in the hippocampus. In conclusion, our findings suggest that 
      chronic treatment with fluoxetine can induce synaptic protein expression by 
      activating the mTOR signaling pathway in a region-dependent manner and mainly in 
      the hippocampus.
FAU - Liu, Xiao-Long
AU  - Liu XL
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
FAU - Luo, Liu
AU  - Luo L
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
FAU - Mu, Rong-Hao
AU  - Mu RH
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
FAU - Liu, Bin-Bin
AU  - Liu BB
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
FAU - Geng, Di
AU  - Geng D
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
FAU - Liu, Qing
AU  - Liu Q
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
FAU - Yi, Li-Tao
AU  - Yi LT
AD  - Department of Chemical and Pharmaceutical Engineering, College of Chemical 
      Engineering, Huaqiao University, Xiamen 361021, Fujian province, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151102
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antidepressive Agents)
RN  - 0 (Synapsins)
RN  - 01K63SUP8D (Fluoxetine)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amygdala/drug effects/metabolism
MH  - Animals
MH  - Antidepressive Agents/*pharmacology
MH  - Depression/*drug therapy/*metabolism
MH  - Fluoxetine/*pharmacology
MH  - Frontal Lobe/drug effects/metabolism
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Phosphorylation/drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - Stress, Psychological/metabolism
MH  - Synapsins/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC4629199
COIS- The authors declare no competing financial interests.
EDAT- 2015/11/03 06:00
MHDA- 2016/09/14 06:00
PMCR- 2015/11/02
CRDT- 2015/11/03 06:00
PHST- 2015/04/23 00:00 [received]
PHST- 2015/10/08 00:00 [accepted]
PHST- 2015/11/03 06:00 [entrez]
PHST- 2015/11/03 06:00 [pubmed]
PHST- 2016/09/14 06:00 [medline]
PHST- 2015/11/02 00:00 [pmc-release]
AID - srep16024 [pii]
AID - 10.1038/srep16024 [doi]
PST - epublish
SO  - Sci Rep. 2015 Nov 2;5:16024. doi: 10.1038/srep16024.