PMID- 25586993
OWN - NLM
STAT- MEDLINE
DCOM- 20150903
LR  - 20181113
IS  - 1759-0914 (Electronic)
IS  - 1759-0914 (Linking)
VI  - 7
IP  - 1
DP  - 2015 Jan-Feb
TI  - Brain-derived neurotrophic factor deficiency restricts proliferation of 
      oligodendrocyte progenitors following cuprizone-induced demyelination.
LID - 10.1177/1759091414566878 [doi]
LID - 1759091414566878
AB  - Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family 
      of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 
      (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in 
      oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well 
      understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice 
      following cuprizone-elicited demyelination. Here, we investigate whether these 
      blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ 
      and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects 
      on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRalpha)+ or NG2+ 
      cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine (EdU) was 
      injected intraperitoneally and colocalized with PDGFRalpha+ cells. Alternatively, 
      proliferating cell nuclear antigen (PCNA) was colocalized with PDGFRalpha or NG2. 
      Labeling indices were determined in the BDNF+/+ and BDNF+/- animals. After 4 or 5 
      weeks of control feed, BDNF+/- mice exhibit similar numbers of OPCs compared with 
      BDNF+/+ animals. The labeling indices for EdU and PCNA also were not 
      significantly different, suggesting that neither the DNA synthesis phase (S 
      phase) nor the proliferative pool size was different between genotypes. In 
      contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in 
      OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference 
      in elevations in cell number was accompanied by decreases in EdU labeling and 
      PCNA labeling without changes in cell death, indicating a reduction in the DNA 
      synthesis and the proliferative pool. Therefore, levels of BDNF influence the 
      proliferation of OPCs resulting from a demyelinating lesion.
CI  - (c) The Author(s) 2015.
FAU - Tsiperson, Vladislav
AU  - Tsiperson V
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA.
FAU - Huang, Yangyang
AU  - Huang Y
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA.
FAU - Bagayogo, Issa
AU  - Bagayogo I
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA.
FAU - Song, Yeri
AU  - Song Y
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA.
FAU - VonDran, Melissa W
AU  - VonDran MW
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA.
FAU - DiCicco-Bloom, Emanuel
AU  - DiCicco-Bloom E
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA.
FAU - Dreyfus, Cheryl F
AU  - Dreyfus CF
AD  - Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical 
      School, Rutgers University, Piscataway, NJ, USA dreyfus@rwjms.rutgers.edu.
LA  - eng
GR  - R01 NS036647/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150113
PL  - United States
TA  - ASN Neuro
JT  - ASN neuro
JID - 101507115
RN  - 0 (Antigens)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Monoamine Oxidase Inhibitors)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Proliferating Cell Nuclear Antigen)
RN  - 0 (Proteoglycans)
RN  - 0 (chondroitin sulfate proteoglycan 4)
RN  - 54924-46-8 (ethylene diurea)
RN  - 5N16U7E0AO (Cuprizone)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
RN  - G34N38R2N1 (Bromodeoxyuridine)
SB  - IM
MH  - Animals
MH  - Antigens/metabolism
MH  - Brain-Derived Neurotrophic Factor/*deficiency/genetics
MH  - Bromodeoxyuridine/metabolism
MH  - Cell Proliferation/drug effects/*genetics
MH  - Cuprizone/toxicity
MH  - Demyelinating Diseases/chemically induced/*pathology
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/drug effects/*genetics
MH  - In Situ Nick-End Labeling
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Monoamine Oxidase Inhibitors/toxicity
MH  - Oligodendroglia/*physiology
MH  - Phenylurea Compounds
MH  - Proliferating Cell Nuclear Antigen/metabolism
MH  - Proteoglycans/metabolism
MH  - Receptor, Platelet-Derived Growth Factor alpha/metabolism
MH  - Stem Cells/drug effects/*metabolism
MH  - Time Factors
PMC - PMC4720179
OTO - NOTNLM
OT  - BDNF
OT  - DNA synthesis
OT  - PDGFRalpha
OT  - corpus callosum
OT  - cuprizone-induced demyelination
OT  - oligodendrocyte progenitors
EDAT- 2015/01/15 06:00
MHDA- 2015/09/04 06:00
PMCR- 2015/01/12
CRDT- 2015/01/15 06:00
PHST- 2015/01/15 06:00 [entrez]
PHST- 2015/01/15 06:00 [pubmed]
PHST- 2015/09/04 06:00 [medline]
PHST- 2015/01/12 00:00 [pmc-release]
AID - 7/1/1759091414566878 [pii]
AID - 10.1177_1759091414566878 [pii]
AID - 10.1177/1759091414566878 [doi]
PST - epublish
SO  - ASN Neuro. 2015 Jan 13;7(1):1759091414566878. doi: 10.1177/1759091414566878. 
      Print 2015 Jan-Feb.