PMID- 24597481
OWN - NLM
STAT- MEDLINE
DCOM- 20140916
LR  - 20211021
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 11
DP  - 2014 Mar 6
TI  - Extensive dysregulations of oligodendrocytic and astrocytic connexins are 
      associated with disease progression in an amyotrophic lateral sclerosis mouse 
      model.
PG  - 42
LID - 10.1186/1742-2094-11-42 [doi]
AB  - BACKGROUND: Non-cell-autonomous motor neuronal death is suggested in a mutant 
      Cu/Zn superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis (ALS) 
      model, in which glial cells play significant roles in disease progression. 
      Connexins (Cxs) form homotypic or heterotypic gap junctions (GJs) and allow 
      direct intercellular communications among nervous tissue cells. The role of Cxs 
      in motor neuron disease has never been investigated; therefore, we aimed to 
      evaluate alterations of Cxs in mSOD1-transgenic (mSOD1-Tg) mice in comparison 
      with their non-transgenic (non-Tg) littermates at the same ages. METHODS: We 
      pathologically evaluated temporal changes to astrocytic Cx43/Cx30 and 
      oligodendrocytic Cx47/Cx32 immunoreactivities at presymptomatic, 
      disease-progressive, and end stages, relative to aquaporin-4 (AQP4), glial 
      fibrillary acidic protein (GFAP), excitatory amino acid transporter-2 (EAAT2), 
      myelin-oligodendrocyte glycoprotein (MOG), and Nogo-A immunoreactivities, and 
      observed neuronal loss by NeuN and neurofilament immunostaining, and microglial 
      response by Iba-1 immunostaining. We also performed quantitative immunoblotting 
      and real-time PCR analyses for Cxs. RESULTS: The mSOD1-Tg mice showed neuronal 
      and axonal loss in the anterior horns of the lumbar spinal cord accompanied by 
      increased activation of microglia compared with non-Tg mice at the 
      disease-progressive and end stages. Expression patterns of Cxs were not different 
      between mSOD1-Tg and non-Tg mice at the presymptomatic stage, but 
      immunoreactivities for GFAP, Cx43, Cx30 and AQP4 were increased in the anterior 
      horns of mSOD1-Tg mice at the disease-progressive and end stages. By contrast, 
      Cx47 and Cx32 immunoreactivities were markedly diminished in Nogo-A-positive 
      oligodendrocytes in the anterior horns of mSOD1-Tg mice at the 
      disease-progressive and end stages, especially in oligodendrocytes showing SOD1 
      accumulation. EAAT2 immunoreactivity was also diminished in the anterior horns of 
      mSOD1-Tg mice at the disease-progressive and end stages. Quantitative 
      immunoblotting revealed a significant reduction in Cx47 and Cx32 protein levels 
      in mSOD1-Tg mice at the disease-progressive and end stages. The levels of Cx47 
      and Cx32 mRNAs were also decreased at these stages. CONCLUSIONS: Our findings 
      indicate that oligodendrocytic and astrocytic GJ proteins in the anterior horns 
      of spinal cord in mSOD1-Tg mice are profoundly affected at the 
      disease-progressive and end stages, where disruption of GJs among glial cells may 
      exacerbate motor neuronal death.
FAU - Cui, Yiwen
AU  - Cui Y
FAU - Masaki, Katsuhisa
AU  - Masaki K
FAU - Yamasaki, Ryo
AU  - Yamasaki R
FAU - Imamura, Shihoko
AU  - Imamura S
FAU - Suzuki, Satoshi O
AU  - Suzuki SO
FAU - Hayashi, Shintaro
AU  - Hayashi S
FAU - Sato, Shinya
AU  - Sato S
FAU - Nagara, Yuko
AU  - Nagara Y
FAU - Kawamura, Mami F
AU  - Kawamura MF
FAU - Kira, Jun-ichi
AU  - Kira J
AD  - Department of Neurology, Neurological Institute, Graduate School of Medical 
      Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. 
      kira@neuro.med.kyushu-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140306
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Aqp4 protein, mouse)
RN  - 0 (Aquaporin 4)
RN  - 0 (Connexins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (RNA, Messenger)
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/genetics/*pathology
MH  - Animals
MH  - Aquaporin 4/metabolism
MH  - Astrocytes/*metabolism
MH  - Connexins/*metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Gene Expression Regulation/*genetics
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Confocal
MH  - Oligodendroglia/*metabolism
MH  - RNA, Messenger
MH  - Spinal Cord/metabolism/pathology
MH  - Superoxide Dismutase/genetics
PMC - PMC4016493
EDAT- 2014/03/07 06:00
MHDA- 2014/09/17 06:00
PMCR- 2014/03/06
CRDT- 2014/03/07 06:00
PHST- 2013/11/14 00:00 [received]
PHST- 2014/02/25 00:00 [accepted]
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2014/09/17 06:00 [medline]
PHST- 2014/03/06 00:00 [pmc-release]
AID - 1742-2094-11-42 [pii]
AID - 10.1186/1742-2094-11-42 [doi]
PST - epublish
SO  - J Neuroinflammation. 2014 Mar 6;11:42. doi: 10.1186/1742-2094-11-42.