PMID- 25101702
OWN - NLM
STAT- MEDLINE
DCOM- 20141217
LR  - 20171116
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 73
IP  - 9
DP  - 2014 Sep
TI  - Oligodendrocyte gap junction loss and disconnection from reactive astrocytes in 
      multiple sclerosis gray matter.
PG  - 865-79
LID - 10.1097/NEN.0000000000000106 [doi]
AB  - Gap junctions are essential for glial cell function and have been increasingly 
      implicated in multiple sclerosis (MS). Because increasing cortical abnormalities 
      correlate with disease progression and cognitive dysfunction, we examined the 
      expression of oligodendrocytic connexin32 (Cx32) and Cx47 and their astrocytic 
      partners Cx30 and Cx43 in cortical lesions and normal-appearing gray matter 
      (NAGM) in MS patients. Postmortem brain tissue samples from 9 MS cases were 
      compared with 10 controls using real-time polymerase chain reaction, immunoblot, 
      and immunohistochemical analyses. Connexin32 and Cx47 gap junction formation in 
      oligodendrocytes was reduced within lesions, whereas Cx32 loss also extended to 
      NAGM. In contrast, astrocytic Cx30 expression was increased within cortical 
      lesions, whereas Cx43 was elevated in both lesions and NAGM. Diffuse microglial 
      activation and marked astrogliotic changes accompanied these connexin 
      abnormalities. Increased expression of Cx43 correlated with inflammatory load (r 
      = 0.828, p = 0.042), whereas Cx32 expression correlated with longer disease 
      duration and, therefore, milder course (r = 0.825, p = 0.043). Thus, there is a 
      loss of intramyelin and intercellular oligodendrocyte gap junctions in MS gray 
      matter lesions and NAGM, whereas interastrocytic gap junctions are increased, 
      reflecting astrogliosis. These changes correlate with inflammation and disease 
      duration and suggest that disconnection of oligodendrocytes from reactive 
      astrocytes may play a role in failed remyelination and disease progression.
FAU - Markoullis, Kyriaki
AU  - Markoullis K
AD  - From the Neuroscience Laboratory (KM, IS, NS, KAK) and Neurology Clinics (KAK), 
      The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; and Wolfson 
      Neuroscience Laboratories, Division of Brain Sciences, Imperial College Faculty 
      of Medicine, London, United Kingdom (FR, RR).
FAU - Sargiannidou, Irene
AU  - Sargiannidou I
FAU - Schiza, Natasa
AU  - Schiza N
FAU - Roncaroli, Federico
AU  - Roncaroli F
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
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Antigens, CD)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Connexins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (OLIG2 protein, human)
RN  - 0 (Oligodendrocyte Transcription Factor 2)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antigens, CD/metabolism
MH  - Astrocytes/*pathology
MH  - Basic Helix-Loop-Helix Transcription Factors/metabolism
MH  - Connexins/genetics/metabolism
MH  - Female
MH  - Gap Junctions/metabolism/*pathology
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Gray Matter/*pathology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Multiple Sclerosis/*pathology
MH  - Nerve Tissue Proteins/metabolism
MH  - Oligodendrocyte Transcription Factor 2
MH  - Oligodendroglia/*pathology
MH  - Plaque, Amyloid/etiology
MH  - RNA, Messenger/metabolism
EDAT- 2014/08/08 06:00
MHDA- 2014/12/18 06:00
CRDT- 2014/08/08 06:00
PHST- 2014/08/08 06:00 [entrez]
PHST- 2014/08/08 06:00 [pubmed]
PHST- 2014/12/18 06:00 [medline]
AID - 10.1097/NEN.0000000000000106 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2014 Sep;73(9):865-79. doi: 
      10.1097/NEN.0000000000000106.