PMID- 27904994
OWN - NLM
STAT- MEDLINE
DCOM- 20180713
LR  - 20220408
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 37
IP  - 7
DP  - 2017 Oct
TI  - Rapamycin Protects Sepsis-Induced Cognitive Impairment in Mouse Hippocampus by 
      Enhancing Autophagy.
PG  - 1195-1205
LID - 10.1007/s10571-016-0449-x [doi]
AB  - The purpose of this study is to test the hypothesis that the mammalian target of 
      rapamycin (mTOR) signaling pathway might mediate neuroprotection in a mouse model 
      of septic encephalopathy and also to identify the role of autophagy. Mice were 
      subjected to cecal ligation and puncture (CLP) or a sham operation, and all 50 
      mice were randomly assigned to five groups: sham, CLP+ saline, CLP+ rapamycin (1, 
      5, 10 mg/kg) groups. Two weeks after the operation, Morris water maze was 
      conducted for behavioral test; Nissl staining was used for observing glia 
      infiltration; immunohistochemical staining and biochemical measures in hippocampi 
      were performed to detect mTOR targets and autophagy indicators. Immunochemistry 
      revealed significant loss of neurons and increased glia infiltration in 
      hippocampus after CLP operation. Inhibition of mTOR by rapamycin rescued 
      cognitive deficits caused by sepsis (p < 0.05). Rapamycin did not affect total 
      mTOR targets, while phosphorylated mTOR targets (p-mTOR-Ser2448, p-p70S6k-Thr389, 
      p-AKT-S473) decreased (p < 0.05) and autophagy indicators (LC3-II, Atg5, Atg7) 
      were increased, and P62 was decreased in rapamycin-treated CLP mice compared with 
      the untreated (p < 0.05) in hippocampus. Rapamycin improves learning after sepsis 
      through enhancing autophagy and may be a potentially effective therapeutic agent 
      for the treatment of sepsis-induced cognitive impairment.
FAU - Liu, Wenyu
AU  - Liu W
AD  - Departments of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue 
      Alley, Chengdu, 610041, China.
FAU - Guo, Jia'nan
AU  - Guo J
AD  - Departments of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue 
      Alley, Chengdu, 610041, China.
FAU - Mu, Jie
AU  - Mu J
AD  - Departments of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue 
      Alley, Chengdu, 610041, China.
FAU - Tian, Linyu
AU  - Tian L
AD  - Departments of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue 
      Alley, Chengdu, 610041, China. tianlinyu@sina.com.
FAU - Zhou, Dong
AU  - Zhou D
AD  - Departments of Neurology, West China Hospital, Sichuan University, No. 37 GuoXue 
      Alley, Chengdu, 610041, China. zhoudong66@yahoo.de.
LA  - eng
PT  - Journal Article
DEP - 20161201
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Autophagy/drug effects/*physiology
MH  - Cognitive Dysfunction/pathology/*prevention & control
MH  - Hippocampus/*drug effects/pathology
MH  - Male
MH  - Mice
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Sepsis-Associated Encephalopathy/pathology/*prevention & control
MH  - Sirolimus/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
OTO - NOTNLM
OT  - Autophagy
OT  - Cognitive impairment
OT  - Hippocampus
OT  - Mammalian target of rapamycin (mTOR)
OT  - Sepsis
EDAT- 2016/12/03 06:00
MHDA- 2018/07/14 06:00
CRDT- 2016/12/02 06:00
PHST- 2016/06/09 00:00 [received]
PHST- 2016/11/23 00:00 [accepted]
PHST- 2016/12/03 06:00 [pubmed]
PHST- 2018/07/14 06:00 [medline]
PHST- 2016/12/02 06:00 [entrez]
AID - 10.1007/s10571-016-0449-x [pii]
AID - 10.1007/s10571-016-0449-x [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2017 Oct;37(7):1195-1205. doi: 10.1007/s10571-016-0449-x. 
      Epub 2016 Dec 1.