PMID- 26910914
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 11
DP  - 2016 Mar 15
TI  - CCR5 deficiency accelerates lipopolysaccharide-induced astrogliosis, amyloid-beta 
      deposit and impaired memory function.
PG  - 11984-99
LID - 10.18632/oncotarget.7453 [doi]
AB  - Chemokine receptors are implicated in inflammation and immune responses. 
      Neuro-inflammation is associated with activation of astrocyte and amyloid-beta 
      (Abeta) generations that lead to pathogenesis of Alzheimer disease (AD). Previous 
      our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in 
      activation of astrocytes and Abeta deposit, and thus memory dysfunction through 
      increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were 
      used as an animal model with memory dysfunction. For the purpose LPS was injected 
      i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in 
      LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as 
      non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS 
      injected CCR5 knockout mice, LPS injection significant increase expression of 
      inflammatory proteins, astrocyte activation, expressions of beta-secretase as well 
      as Abeta deposition in the brain of CCR5 knockout mice as compared with that of CCR5 
      wild type mice. In CCR5 knockout mice, CCR2 expressions were high and 
      co-localized with GFAP which was significantly elevated by LPS. Expression of 
      monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased 
      by LPS injection, and increment of MCP-1 expression is much higher in CCR5 
      knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide 
      (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS 
      (1 mug/ml) and CCR2 antagonist, decreased the NF-A B activation and Abeta level. 
      These findings suggest that the deficiency of CCR5 enhances response of LPS, 
      which accelerates to neuro-inflammation and memory impairment.
FAU - Hwang, Chul Ju
AU  - Hwang CJ
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Park, Mi Hee
AU  - Park MH
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Hwang, Jae Yeon
AU  - Hwang JY
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Kim, Ju Hwan
AU  - Kim JH
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Yun, Na Young
AU  - Yun NY
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Oh, Sang Yeon
AU  - Oh SY
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Song, Ju Kyung
AU  - Song JK
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Seo, Hyun Ok
AU  - Seo HO
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Kim, Yun-Bae
AU  - Kim YB
AD  - College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic 
      of Korea.
FAU - Hwang, Dae Yeon
AU  - Hwang DY
AD  - College of Natural Resources and Life Science, Pusan National University, Pusan, 
      Republic of Korea.
FAU - Oh, Ki-Wan
AU  - Oh KW
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Han, Sang-Bae
AU  - Han SB
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
FAU - Hong, Jin Tae
AU  - Hong JT
AD  - College of Pharmacy and Medical Research Center, Chungbuk National University, 
      Cheongju, Republic of Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (CCR5 protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, CCR5)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Astrocytes/drug effects/*pathology
MH  - Behavior, Animal
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Gliosis/*etiology/pathology
MH  - Inflammation/chemically induced/*complications
MH  - Lipopolysaccharides/*toxicity
MH  - Male
MH  - Memory Disorders/*etiology/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Plaque, Amyloid/*etiology/pathology
MH  - Receptors, CCR5/*physiology
PMC - PMC4914263
OTO - NOTNLM
OT  - Alzheimer's disease (AD)
OT  - Amyloid beta (Abeta)
OT  - CC chemokine receptor 2 (CCR2)
OT  - CC chemokine receptor 5 (CCR5)
OT  - Pathology Section
OT  - memory impairment
COIS- CONFLICTS OF INTEREST The authors declare no competing financial interests.
EDAT- 2016/02/26 06:00
MHDA- 2017/12/12 06:00
PMCR- 2016/03/15
CRDT- 2016/02/25 06:00
PHST- 2015/08/30 00:00 [received]
PHST- 2016/02/05 00:00 [accepted]
PHST- 2016/02/25 06:00 [entrez]
PHST- 2016/02/26 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2016/03/15 00:00 [pmc-release]
AID - 7453 [pii]
AID - 10.18632/oncotarget.7453 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Mar 15;7(11):11984-99. doi: 10.18632/oncotarget.7453.