PMID- 28431607
OWN - NLM
STAT- MEDLINE
DCOM- 20180221
LR  - 20231213
IS  - 1878-5883 (Electronic)
IS  - 0022-510X (Linking)
VI  - 376
DP  - 2017 May 15
TI  - Sigma-1 receptor in brain ischemia/reperfusion: Possible role in the NR2A-induced 
      pathway to regulate brain-derived neurotrophic factor.
PG  - 166-175
LID - S0022-510X(17)30196-X [pii]
LID - 10.1016/j.jns.2017.03.027 [doi]
AB  - Sigma-1 receptor (sigma1r) activation could attenuate the learning and memory 
      deficits in the AD model, ischemia model and others. In our previous study, the 
      activation of sigma1r increased the expression of brain-derived neurotrophic factor 
      (BDNF), possibly through the NR2A-induced pathway, and sigma1r agonists might 
      function as neuroprotectant agents in vascular dementia. Here, we used sigma1r 
      knockout mice to confirm the role of sigma1r. Furthermore, an antagonist of NR2A was 
      first used to investigate whether the NR2A-induced pathway is the necessary link 
      between sigma1r and BDNF. The operation of brain ischemia/reperfusion was induced by 
      bilateral common carotid artery occlusion for 20min in C57BL/6 and sigma1r knockout 
      mice as the ischemic group. A sigma1r agonist, PRE084 (1mg/kg, i.p.), and NR2A 
      antagonist, PEAQX (10mg/kg, i.p.), were administered once daily throughout the 
      experiment. Behavioral tests were performed starting on day 8. On day 22 after 
      brain ischemia/reperfusion, mice were sacrificed and brains were immediately 
      collected and the injured and the hippocampus was isolated and stored at -80 degrees C 
      for western blot analysis. After ischemic operation, contrast with the sigma1r 
      knockout mice, PRE084 significantly ameliorated learning and memory impairments 
      in the behavioral evaluation, and prevented the protein decline of BDNF, NR2A, 
      CaMKIV and TORC1 expression in wild-type mice. However, the effects of PRE084 on 
      CaMKIV-TORC1-CREB and BDNF, even for learning and memory impairment, were 
      antagonized by the co-administration of PEAQX, an antagonist of NR2A. The 
      activation of sigma1r improves the impairment of learning and memory in the 
      ischemia/reperfusion model, and the expression of BDNF, which may have been 
      achieved through the NR2A-CaMKIV-TORC1 pathway.
CI  - Copyright (c) 2017. Published by Elsevier B.V.
FAU - Xu, Qian
AU  - Xu Q
AD  - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang 
      Pharmaceutical University, Shenyang 110016, China.
FAU - Ji, Xue-Fei
AU  - Ji XF
AD  - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang 
      Pharmaceutical University, Shenyang 110016, China.
FAU - Chi, Tian-Yan
AU  - Chi TY
AD  - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang 
      Pharmaceutical University, Shenyang 110016, China.
FAU - Liu, Peng
AU  - Liu P
AD  - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang 
      Pharmaceutical University, Shenyang 110016, China.
FAU - Jin, Ge
AU  - Jin G
AD  - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang 
      Pharmaceutical University, Shenyang 110016, China.
FAU - Chen, Ling
AU  - Chen L
AD  - Department of Physiology, Nanjing Medical University, Nanjing 210029, China. 
      Electronic address: lingchen@njmu.edu.cn.
FAU - Zou, Li-Bo
AU  - Zou LB
AD  - Department of Pharmacology, School of Life Science and Biopharmaceutics, Shenyang 
      Pharmaceutical University, Shenyang 110016, China. Electronic address: 
      libozou@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170319
PL  - Netherlands
TA  - J Neurol Sci
JT  - Journal of the neurological sciences
JID - 0375403
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (NR2A NMDA receptor)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, sigma)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 4)
RN  - EC 2.7.11.17 (Camk4 protein, mouse)
SB  - IM
MH  - Animals
MH  - Brain/drug effects/*metabolism/pathology
MH  - Brain Ischemia/drug therapy/*metabolism/pathology/psychology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 4/metabolism
MH  - Cognitive Dysfunction/drug therapy/etiology/metabolism/pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Hippocampus/drug effects/metabolism/pathology
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Memory/drug effects/physiology
MH  - Memory Disorders/drug therapy/etiology/metabolism/pathology
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/drug effects/metabolism/pathology
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*metabolism
MH  - Receptors, sigma/agonists/genetics/*metabolism
MH  - Reperfusion Injury/drug therapy/*metabolism/pathology/psychology
MH  - Sigma-1 Receptor
OTO - NOTNLM
OT  - Brain ischemia/reperfusion
OT  - Brain-derived neurotrophic factor
OT  - NR2A-CaMKIV-TORC1
OT  - PEAQX
OT  - Sigma-1 receptor
EDAT- 2017/04/23 06:00
MHDA- 2018/02/22 06:00
CRDT- 2017/04/23 06:00
PHST- 2016/09/17 00:00 [received]
PHST- 2017/02/18 00:00 [revised]
PHST- 2017/03/17 00:00 [accepted]
PHST- 2017/04/23 06:00 [entrez]
PHST- 2017/04/23 06:00 [pubmed]
PHST- 2018/02/22 06:00 [medline]
AID - S0022-510X(17)30196-X [pii]
AID - 10.1016/j.jns.2017.03.027 [doi]
PST - ppublish
SO  - J Neurol Sci. 2017 May 15;376:166-175. doi: 10.1016/j.jns.2017.03.027. Epub 2017 
      Mar 19.