PMID- 22461072
OWN - NLM
STAT- MEDLINE
DCOM- 20120920
LR  - 20231213
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 60
IP  - 7
DP  - 2012 Jul
TI  - Disruption of oligodendrocyte gap junctions in experimental autoimmune 
      encephalomyelitis.
PG  - 1053-66
LID - 10.1002/glia.22334 [doi]
AB  - Gap junctions (GJs) are vital for oligodendrocyte survival and myelination. In 
      order to examine how different stages of inflammatory demyelination affect 
      oligodendrocyte GJs, we studied the expression of oligodendrocytic connexin32 
      (Cx32) and Cx47 and astrocytic Cx43 in the experimental autoimmune 
      encephalomyelitis (EAE) mouse model of multiple sclerosis (MS) induced by 
      recombinant myelin oligodendrocyte glycoprotein. EAE was characterized by 
      remissions and relapses with demyelination and axonal loss. Formation of GJ 
      plaques was quantified in relation to the lesions and in normal appearing white 
      matter (NAWM). During acute EAE at 14 days postimmunization (dpi) both Cx47 and 
      Cx32 GJs were severely reduced within and around lesions but also in the NAWM. 
      Cx47 was localized intracellularly in oligodendrocytes while protein levels 
      remained unchanged, and this redistribution coincided with the loss of Cx43 GJs 
      in astrocytes. Cx47 and Cx32 expression increased during remyelination at 28 dpi 
      but decreased again at 50 dpi in the relapsing phase. Oligodendrocyte GJs 
      remained reduced even in NAWM, despite increased formation of Cx43 GJs toward 
      lesions indicating astrogliosis. EAE induced in Cx32 knockout mice resulted in an 
      exacerbated clinical course with more demyelination and axonal loss compared with 
      wild-type EAE mice of the same backcross, despite similar degree of inflammation, 
      and an overall milder loss of Cx47 and Cx43 GJs. Thus, EAE causes persistent 
      impairment of both intra- and intercellular oligodendrocyte GJs even in the NAWM, 
      which may be an important mechanism of MS progression. Furthermore, GJ deficient 
      myelinated fibers appear more vulnerable to CNS inflammatory demyelination.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Markoullis, Kyriaki
AU  - Markoullis K
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics, Nicosia, 
      Cyprus.
FAU - Sargiannidou, Irene
AU  - Sargiannidou I
FAU - Gardner, Christopher
AU  - Gardner C
FAU - Hadjisavvas, Andreas
AU  - Hadjisavvas A
FAU - Reynolds, Richard
AU  - Reynolds R
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120327
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (connexin 47)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism/pathology
MH  - Axons/metabolism/pathology
MH  - Connexin 43/metabolism
MH  - Connexins/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/metabolism/*pathology
MH  - Female
MH  - Gap Junctions/metabolism/*pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Oligodendroglia/metabolism/*pathology
MH  - Gap Junction beta-1 Protein
EDAT- 2012/03/31 06:00
MHDA- 2012/09/21 06:00
CRDT- 2012/03/31 06:00
PHST- 2012/01/05 00:00 [received]
PHST- 2012/03/05 00:00 [accepted]
PHST- 2012/03/31 06:00 [entrez]
PHST- 2012/03/31 06:00 [pubmed]
PHST- 2012/09/21 06:00 [medline]
AID - 10.1002/glia.22334 [doi]
PST - ppublish
SO  - Glia. 2012 Jul;60(7):1053-66. doi: 10.1002/glia.22334. Epub 2012 Mar 27.