PMID- 26851069
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20161230
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 121
DP  - 2016 Mar
TI  - TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation 
      induced by systemic LPS administration.
PG  - 192-200
LID - S0361-9230(16)30014-4 [pii]
LID - 10.1016/j.brainresbull.2016.02.001 [doi]
AB  - Translocator protein 18 kDa (TSPO) is now an attractive drug target for 
      controlling neuroinflammation. Studies applying TSPO ligands to neurodegenerative 
      diseases, especially Alzheimer's disease (AD), were rare. Our study was aimed to 
      evaluate the effect of PK11195, a specific TSPO ligand, in an animal model of 
      neuroinflammation caused by systemic LPS administration. C57/BL6 mice were 
      treated with lipopolysaccharide (LPS, 500 mug/kg, i.p.) three days after PK11195 
      administration (3mg/kg, i.p.). The drugs were not discontinued until the mice 
      were sacrificed. Cognitive function was assessed by Morris water maze (MWM) seven 
      days after LPS injection. Chronic LPS-injection in mice was characterized by 
      cognitive dysfunction, increased expression of cyclooxygenase (COX)-2 and TSPO, 
      elevated Abeta content with increased expression of beta-site APP cleaving enzyme-1 
      (BACE-1) and insulin-degrading enzyme (IDE) as well as decreased brain 
      progesterone and brain-derived neurophic factor (BDNF) level. PK11195 
      pretreatment protected cognitive function in LPS-injected animals and normalized 
      the inflammatory proteins. Moreover, PK11195 pre-administration decreased 
      elevated hippocampal Abetax-42 levels and increased brain levels of progesterone, 
      allopregnanolone. However, LPS-induced BDNF decrease was not reversed by PK11195 
      administration. Our data demonstrated that PK11195 could protect cognitive 
      deficits induced by chronic LPS administration. The underling mechanism may 
      involve alleviated neuroinflammation, increased synthesis of neurosteroid and 
      decreased Abeta accumulation accompanied by down-regulation of BACE-1.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Ma, Li
AU  - Ma L
AD  - Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, 
      China; Department of Anesthesiology, General Hospital of Beijing Military 
      Command, Beijing 100700, China.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Department of Neurosurgery, Air Force General Hospital of the Chinese People's 
      Liberation Army, Beijing 100142, China.
FAU - Liu, Na
AU  - Liu N
AD  - Department of Anesthesiology, Affiliated Hospital of Chengde Mdical University, 
      Chengde 067000, China.
FAU - Wang, Pei-qi
AU  - Wang PQ
AD  - Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Guo, Wen-zhi
AU  - Guo WZ
AD  - Department of Anesthesiology, General Hospital of Beijing Military Command, 
      Beijing 100700, China.
FAU - Fu, Qiang
AU  - Fu Q
AD  - Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, 
      China.
FAU - Jiao, Lin-bo
AU  - Jiao LB
AD  - Department of Anesthesiology, General Hospital of Beijing Military Command, 
      Beijing 100700, China.
FAU - Ma, Ya-qun
AU  - Ma YQ
AD  - Department of Anesthesiology, General Hospital of Beijing Military Command, 
      Beijing 100700, China.
FAU - Mi, Wei-Dong
AU  - Mi WD
AD  - Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, 
      China. Electronic address: mi_wd301@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160202
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Bzrp protein, mouse)
RN  - 0 (Isoquinolines)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, GABA)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - BXO86P3XXW (Pregnanolone)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
RN  - YNF83VN1RL (PK 11195)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/genetics/metabolism
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Aspartic Acid Endopeptidases/genetics/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Encephalitis/chemically induced/*drug therapy/metabolism/pathology
MH  - Gene Expression Regulation/*drug effects
MH  - Hippocampus/drug effects/metabolism
MH  - Isoquinolines/*therapeutic use
MH  - Lipopolysaccharides/toxicity
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pregnanolone/metabolism
MH  - Progesterone/metabolism
MH  - Receptors, GABA/metabolism
OTO - NOTNLM
OT  - Cognition
OT  - LPS
OT  - Neuroinflammation
OT  - Neurosteroid
OT  - PK11195
OT  - TSPO
EDAT- 2016/02/07 06:00
MHDA- 2016/12/15 06:00
CRDT- 2016/02/07 06:00
PHST- 2015/12/21 00:00 [received]
PHST- 2016/01/26 00:00 [revised]
PHST- 2016/02/01 00:00 [accepted]
PHST- 2016/02/07 06:00 [entrez]
PHST- 2016/02/07 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
AID - S0361-9230(16)30014-4 [pii]
AID - 10.1016/j.brainresbull.2016.02.001 [doi]
PST - ppublish
SO  - Brain Res Bull. 2016 Mar;121:192-200. doi: 10.1016/j.brainresbull.2016.02.001. 
      Epub 2016 Feb 2.