PMID- 24252211
OWN - NLM
STAT- MEDLINE
DCOM- 20150331
LR  - 20211021
IS  - 2051-5960 (Electronic)
IS  - 2051-5960 (Linking)
VI  - 1
DP  - 2013 Jun 4
TI  - MCP-1/CCR2 signaling-mediated astrocytosis is accelerated in a transgenic mouse 
      model of SOD1-mutated familial ALS.
PG  - 21
LID - 10.1186/2051-5960-1-21 [doi]
AB  - BACKGROUND: Emerging evidence suggests that innate immunity and increased 
      oxidative stress contribute to pathomechanisms in amyotrophic lateral sclerosis 
      (ALS). The aim of the present study was to verify the involvement of monocyte 
      chemoattractant protein-1 (MCP-1) and its specific CC chemokine receptor 2 (CCR2) 
      in the disease progression of ALS. We here demonstrate the expression state of 
      MCP-1 and CCR2 in lumbar spinal cords of mice overexpressing a transgene for G93A 
      mutant human superoxide dismutase 1 (SOD1) (ALS mice) as a mouse model of ALS as 
      well as the involvement of MCP-1/CCR2-mediated signaling in behavior of cultured 
      astrocytes derived from those mice. RESULTS: Quantitative polymerase chain 
      reaction analysis revealed that MCP-1 and CCR2 mRNA levels were significantly 
      higher in ALS mice than those in nontransgenic littermates (control mice) at the 
      presymptomatic stage. Immunoblot analysis disclosed a significantly higher 
      CCR2/beta-actin optical density ratio in the postsymptomatic ALS mouse group than 
      those in the age-matched control mouse group. Immunohistochemically, MCP-1 
      determinants were mainly localized in motor neurons, while CCR2 determinants were 
      exclusively localized in reactive astrocytes. Primary cultures of astrocytes 
      derived from ALS mice showed a significant increase in proliferation activity 
      under recombinant murine MCP-1 stimuli as compared to those from control mice. 
      CONCLUSIONS: Our results provide in vivo and in vitro evidence that MCP-1 
      stimulates astrocytes via CCR2 to induce astrocytosis in ALS with SOD1 gene 
      mutation. Thus, it is likely that MCP-1/CCR2-mediated sigaling is involved in the 
      disease progression of ALS.
FAU - Kawaguchi-Niida, Motoko
AU  - Kawaguchi-Niida M
AD  - Department of Pathology, Tokyo Women's Medical University, 8-1 Kawada-cho, 
      Shinjuku-ku, Tokyo 162-8666, Japan. mnkawa@research.twmu.ac.jp.
FAU - Yamamoto, Tomoko
AU  - Yamamoto T
FAU - Kato, Yoichiro
AU  - Kato Y
FAU - Inose, Yuri
AU  - Inose Y
FAU - Shibata, Noriyuki
AU  - Shibata N
LA  - eng
PT  - Journal Article
DEP - 20130604
PL  - England
TA  - Acta Neuropathol Commun
JT  - Acta neuropathologica communications
JID - 101610673
RN  - 0 (Actins)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (SOD1 protein, human)
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - Amyotrophic lateral sclerosis 1
SB  - IM
MH  - Actins/metabolism
MH  - Amyotrophic Lateral Sclerosis/*physiopathology
MH  - Animals
MH  - Astrocytes/*physiology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Disease Models, Animal
MH  - Gliosis/*physiopathology
MH  - Lumbar Vertebrae
MH  - Mice, Transgenic
MH  - Motor Neurons/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptors, CCR2/*metabolism
MH  - Signal Transduction
MH  - Spinal Cord/*physiopathology
MH  - Superoxide Dismutase/genetics/metabolism
MH  - Superoxide Dismutase-1
PMC - PMC3893446
EDAT- 2013/11/21 06:00
MHDA- 2013/11/21 06:01
PMCR- 2013/06/04
CRDT- 2013/11/21 06:00
PHST- 2013/04/23 00:00 [received]
PHST- 2013/05/14 00:00 [accepted]
PHST- 2013/11/21 06:00 [entrez]
PHST- 2013/11/21 06:00 [pubmed]
PHST- 2013/11/21 06:01 [medline]
PHST- 2013/06/04 00:00 [pmc-release]
AID - 2051-5960-1-21 [pii]
AID - 10.1186/2051-5960-1-21 [doi]
PST - epublish
SO  - Acta Neuropathol Commun. 2013 Jun 4;1:21. doi: 10.1186/2051-5960-1-21.