PMID- 25611431
OWN - NLM
STAT- MEDLINE
DCOM- 20160115
LR  - 20200225
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 21
IP  - 5
DP  - 2015 May
TI  - Surgical stress induces brain-derived neurotrophic factor reduction and 
      postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation 
      in aged mice.
PG  - 398-409
LID - 10.1111/cns.12368 [doi]
AB  - AIMS: This study explored whether surgical stress-induced glucocorticoid receptor 
      (GR) phosphorylation is related to postoperative cognitive dysfunction (POCD) in 
      aged individuals. Inhibition of GR activation could be an effective treatment for 
      POCD. METHODS: A laparotomy was given to C57/BL6 mice in POCD group both 20 and 6 
      months old. Animals in control group were treated in identical manners except for 
      laparotomy. Cognitive function was evaluated by Morris water maze and elevated 
      plus maze. Western blot and Elisa assay were used to detect related molecules. 
      Mifepristone and roscovitine were treated as inhibitions of GR phosphorylation. 
      RESULTS: The cognitive function was impaired, and brain-derived neurotrophic 
      factor (BDNF) was found reduced in aged POCD group. GR translocation into nucleus 
      and elevated GR phosphorylation were found in prefrontal cortex of aged POCD 
      mice. Cyclin-dependent Kinase 5 (CDK5), kinase for GR phosphorylation also 
      elevated in aged POCD mice. With GR antagonist and CDK5 inhibitor, reduction of 
      BDNF and cognitive dysfunction in aged mice were both rescued. CONCLUSION: These 
      results presented a mechanism that surgical stress-induced GR phosphorylation 
      contributes to POCD in aged individuals. Inhibition of GR activation and 
      phosphorylation might be a potential treatment target of POCD.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Tian, Xiao-Sheng
AU  - Tian XS
AD  - Neuroscience Research Institute & Department of Neurobiology; Health Science 
      Center, Peking University, Beijing, China; Department of Anesthesiology, Peking 
      University Third Hospital, Beijing, China.
FAU - Tong, Ya-Wei
AU  - Tong YW
FAU - Li, Zheng-Qian
AU  - Li ZQ
FAU - Li, Lun-Xu
AU  - Li LX
FAU - Zhang, Tao
AU  - Zhang T
FAU - Ren, Tian-Yun
AU  - Ren TY
FAU - Zhou, Ting
AU  - Zhou T
FAU - Wang, He-Cheng
AU  - Wang HC
FAU - Zhan, Rui
AU  - Zhan R
FAU - Sun, Yang
AU  - Sun Y
FAU - Yan, Zhao
AU  - Yan Z
FAU - Wang, Qiu-Dian
AU  - Wang QD
FAU - Fan, Dong-Sheng
AU  - Fan DS
FAU - Kong, Fan-Jun
AU  - Kong FJ
FAU - Guo, Xiang-Yang
AU  - Guo XY
FAU - Xiao, Wei-Zhong
AU  - Xiao WZ
FAU - Chui, De-Hua
AU  - Chui DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150122
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Receptors, Glucocorticoid)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (Cdk5 protein, mouse)
SB  - IM
MH  - Active Transport, Cell Nucleus/physiology
MH  - Aging/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*deficiency
MH  - Cognition Disorders/etiology/*metabolism
MH  - Cyclin-Dependent Kinase 5/antagonists & inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Laparotomy/adverse effects
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Mice, Inbred C57BL
MH  - Phosphorylation/drug effects
MH  - Postoperative Complications/*metabolism/psychology
MH  - Prefrontal Cortex/drug effects/*metabolism
MH  - Receptors, Glucocorticoid/antagonists & inhibitors/*metabolism
MH  - Stress, Physiological/*physiology
PMC - PMC6495659
OTO - NOTNLM
OT  - Aging
OT  - Brain-derived neurotrophic factor (BDNF)
OT  - GR phosphorylation
OT  - Postoperative cognitive dysfunction (POCD)
OT  - Surgical stress
COIS- The authors declare no conflict of interest.
EDAT- 2015/01/23 06:00
MHDA- 2016/01/16 06:00
PMCR- 2015/01/22
CRDT- 2015/01/23 06:00
PHST- 2014/08/01 00:00 [received]
PHST- 2014/11/01 00:00 [revised]
PHST- 2014/11/02 00:00 [accepted]
PHST- 2015/01/23 06:00 [entrez]
PHST- 2015/01/23 06:00 [pubmed]
PHST- 2016/01/16 06:00 [medline]
PHST- 2015/01/22 00:00 [pmc-release]
AID - CNS12368 [pii]
AID - 10.1111/cns.12368 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2015 May;21(5):398-409. doi: 10.1111/cns.12368. Epub 2015 Jan 
      22.