PMID- 30325069
OWN - NLM
STAT- MEDLINE
DCOM- 20190415
LR  - 20231213
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 66
IP  - 12
DP  - 2018 Dec
TI  - Regulatory role of oligodendrocyte gap junctions in inflammatory demyelination.
PG  - 2589-2603
LID - 10.1002/glia.23513 [doi]
AB  - Gap junctions (GJs) coupling oligodendrocytes to astrocytes and to other 
      oligodendrocytes are formed mainly by connexin47 (Cx47) and a smaller portion by 
      connexin32 (Cx32). Mutations in both connexins cause inherited demyelinating 
      disorders, but their expression is also disrupted in multiple sclerosis (MS). To 
      clarify whether the loss of either Cx47 or Cx32 could modify the outcome of 
      inflammation and myelin loss, we induced experimental autoimmune 
      encephalomyelitis (EAE) in fully backcrossed Cx32 knockout (KO) and Cx47KO mice 
      and compared their outcome with wild type (WT, C57BI/6 N) mice. Cx47KO EAE mice 
      developed the most severe phenotype assessed by clinical scores and behavioral 
      testing, followed by Cx32KO and WT mice. Cx47KO more than Cx32KO EAE mice 
      developed more microglial activation, myelin, and axonal loss than did WT mice. 
      Oligodendrocyte apoptosis and precursor proliferation was also higher in Cx47KO 
      than in Cx32KO or WT EAE mice. Similarly, blood-spinal cord barrier (BSCB) 
      disruption and inflammatory infiltrates of macrophages, T- and B-cells were more 
      severe in Cx47KO than either Cx32KO or WT EAE groups. Finally, expression 
      profiling revealed that several proinflammatory cytokines were higher at the peak 
      of inflammation in the Cx47KO mice and persisted at later stages of EAE in 
      contrast to reduction of their levels in WT EAE mice. Thus, loss of 
      oligodendrocyte GJs aggravates BSCB disruption and inflammatory myelin loss, 
      likely due to dysregulation of proinflammatory cytokines. This mechanism may play 
      an important role in MS brain with reduced connexin expression, as well as in 
      patients with inherited mutations in oligodendrocyte connexins and secondary 
      inflammation.
CI  - (c) 2018 The Authors. Glia published by Wiley Periodicals, Inc.
FAU - Papaneophytou, Christos P
AU  - Papaneophytou CP
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and 
      Cyprus School of Molecular Medicine, Nicosia, Cyprus.
AD  - Department of Life and Health Sciences, School of Sciences and Engineering, 
      University of Nicosia, Nicosia, Cyprus.
FAU - Georgiou, Elena
AU  - Georgiou E
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and 
      Cyprus School of Molecular Medicine, Nicosia, Cyprus.
FAU - Karaiskos, Christos
AU  - Karaiskos C
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and 
      Cyprus School of Molecular Medicine, Nicosia, Cyprus.
FAU - Sargiannidou, Irene
AU  - Sargiannidou I
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and 
      Cyprus School of Molecular Medicine, Nicosia, Cyprus.
FAU - Markoullis, Kyriaki
AU  - Markoullis K
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and 
      Cyprus School of Molecular Medicine, Nicosia, Cyprus.
FAU - Freidin, Mona M
AU  - Freidin MM
AD  - Department of Neurology and Rehabilitation, University of Illinois Chicago, 
      Chicago, Illinois.
FAU - Abrams, Charles K
AU  - Abrams CK
AD  - Department of Neurology and Rehabilitation, University of Illinois Chicago, 
      Chicago, Illinois.
FAU - Kleopa, Kleopas A
AU  - Kleopa KA
AUID- ORCID: 0000-0002-4103-8094
AD  - Neuroscience Laboratory, The Cyprus Institute of Neurology and Genetics and 
      Cyprus School of Molecular Medicine, Nicosia, Cyprus.
AD  - Neurology Clinics, The Cyprus Institute of Neurology and Genetics and Cyprus 
      School of Molecular Medicine, Nicosia, Cyprus.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181016
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Aif1 protein, mouse)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Connexins)
RN  - 0 (Cytokines)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Myelin-Oligodendrocyte Glycoprotein)
RN  - 0 (Peptide Fragments)
RN  - 0 (connexin 47)
RN  - 0 (myelin oligodendrocyte glycoprotein (35-55))
RN  - 9007-81-2 (Freund's Adjuvant)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Astrocytes/metabolism/pathology
MH  - Blood-Brain Barrier/drug effects/physiopathology
MH  - Calcium-Binding Proteins/metabolism
MH  - Cell Proliferation/genetics
MH  - Connexins/genetics/metabolism
MH  - Cytokines/*metabolism
MH  - Disease Models, Animal
MH  - Encephalomyelitis, Autoimmune, Experimental/chemically 
      induced/genetics/*pathology/physiopathology
MH  - Freund's Adjuvant/toxicity
MH  - Gap Junctions/*metabolism/pathology
MH  - Gene Expression Regulation/drug effects/genetics/*physiology
MH  - Hand Strength/*physiology
MH  - Macrophages/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microfilament Proteins/metabolism
MH  - Motor Activity/drug effects/genetics
MH  - Myelin-Oligodendrocyte Glycoprotein/toxicity
MH  - Oligodendroglia/*metabolism/pathology
MH  - Peptide Fragments/toxicity
MH  - Gap Junction beta-1 Protein
PMC - PMC6519212
OTO - NOTNLM
OT  - Connexins
OT  - experimental autoimmune encephalomyelitis
OT  - multiple sclerosis
OT  - myelin
OT  - oligodendrocytes
EDAT- 2018/10/17 06:00
MHDA- 2019/04/16 06:00
PMCR- 2019/05/15
CRDT- 2018/10/17 06:00
PHST- 2018/02/16 00:00 [received]
PHST- 2018/06/20 00:00 [revised]
PHST- 2018/06/25 00:00 [accepted]
PHST- 2018/10/17 06:00 [pubmed]
PHST- 2019/04/16 06:00 [medline]
PHST- 2018/10/17 06:00 [entrez]
PHST- 2019/05/15 00:00 [pmc-release]
AID - GLIA23513 [pii]
AID - 10.1002/glia.23513 [doi]
PST - ppublish
SO  - Glia. 2018 Dec;66(12):2589-2603. doi: 10.1002/glia.23513. Epub 2018 Oct 16.