PMID- 23440860
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20130318
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Linking)
VI  - 61
IP  - 5
DP  - 2013 May
TI  - A functional role of NMDA receptor in regulating the differentiation of 
      oligodendrocyte precursor cells and remyelination.
PG  - 732-49
LID - 10.1002/glia.22469 [doi]
AB  - Differentiation of oligodendrocyte precursor cells (OPCs) is the most important 
      event for the myelination of central nervous system (CNS) axons during 
      development and remyelination in demyelinating diseases, while the underlying 
      molecular mechanisms remain largely unknown. Here we show that NMDA receptor 
      (NMDAR) is a functional regulator of OPCs differentiation and remyelination. 
      First, GluN1, GluN2A, and GluN2B subunits are expressed in oligodendrocyte 
      lineage cells (OLs) in vitro and in vivo by immunostaining and Western blot 
      analysis. Second, in a purified rat OPC culture system, NMDARs specially mediate 
      OPCs differentiation by enhancing myelin proteins expression and the processes 
      branching at the immature to mature oligodendrocyte transition analyzed by a 
      serial of developmental stage-specific antigens. Moreover, pharmacological NMDAR 
      antagonists or specific knockdown of GluN1 by RNA interference in OPCs prevents 
      the differentiation induced by NMDA. NMDA can activate the mammalian target of 
      rapamycin (mTOR) signal in OPCs and the pro-differentiation effect of NMDA is 
      obstructed by the mTOR inhibitor rapamycin, suggesting NMDAR exerts its effect 
      through mTOR-dependent mechanism. Furthermore, NMDA increases numbers of myelin 
      segments in DRG-OPC cocultures. Finally, NMDAR specific antagonist MK801 delays 
      remyelination in the cuprizone model examined by LFB-PAS, immunofluorescence and 
      electron microscopy. This effect appears to result from inhibiting OPCs 
      differentiation as more NG2(+) OPCs but less GST-pi(+) mature oligodendrocytes are 
      observed. Together, these results indicate that NMDAR plays a critical role in 
      the regulation of OPCs differentiation in vitro and remyelination in cuprizone 
      model which may provide potential target for the treatment of demyelination 
      disease.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Li, Cui
AU  - Li C
AD  - Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, 
      Neuroscience Research Center of Changzheng Hospital, Second Military Medical 
      University, Shanghai, 200433, China.
FAU - Xiao, Lin
AU  - Xiao L
FAU - Liu, Xiuyun
AU  - Liu X
FAU - Yang, Wenjing
AU  - Yang W
FAU - Shen, Weiran
AU  - Shen W
FAU - Hu, Chun
AU  - Hu C
FAU - Yang, Guang
AU  - Yang G
FAU - He, Cheng
AU  - He C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130226
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cell Differentiation/drug effects/*physiology
MH  - Cells, Cultured
MH  - Dizocilpine Maleate/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelin Sheath/drug effects/*physiology
MH  - Neural Stem Cells/*cytology/drug effects
MH  - Oligodendroglia/*cytology/drug effects
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/*physiology
EDAT- 2013/02/27 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/02/27 06:00
PHST- 2012/10/03 00:00 [received]
PHST- 2012/12/27 00:00 [accepted]
PHST- 2013/02/27 06:00 [entrez]
PHST- 2013/02/27 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - 10.1002/glia.22469 [doi]
PST - ppublish
SO  - Glia. 2013 May;61(5):732-49. doi: 10.1002/glia.22469. Epub 2013 Feb 26.