Expression of the low-affinity neurotrophin receptor, p75(NTR), is upregulated by oligodendroglial progenitors adjacent to the subventricular zone in response to demyelination.
Precursor cells have the capacity to repopulate the demyelinated brain, but the molecular mechanisms that facilitate their recruitment are largely unknown. The low-affinity neurotrophin receptor, p75(NTR), may be one of these regulators; however, its expression profile by oligodendroglia within the multiple sclerosis (MS) brain remains uncertain. We therefore assessed the expression profile of this receptor within 8 MS and 4 control brains. We found no evidence of expression of p75(NTR) by mature oligodendrocytes. Instead, we demonstrated the presence of p75(NTR) on a subgroup of NG2-positive oligodendroglial progenitors in a periventricular plaque in one MS sample. Notably, p75(NTR)-expressing cells were also detected within the subventricular zone (SVZ) of this brain, adjacent to the periventricular plaque. In animals with experimental demyelination we observed similar patterns of p75(NTR) expression, initially confined to precursor cells within the SVZ, followed at later stages in the disease course by its expression amongst a subset of oligodendroglial progenitors within the corpus callosum. These data suggest that a population of precursor cells within the SVZ can be induced to express p75(NTR) and to subsequently assume an oligodendroglial progenitor phenotype in response to demyelination in the adjacent white matter.
Development and Neurobiology Group, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Post Office, Royal Melbourne Hospital, Victoria, Australia.
Steven
S
Petratos
Michael F
MF
Gonzales
Michael F
MF
Azari
Mark
M
Marriott
Rebecca A
RA
Minichiello
Kylie A
KA
Shipham
Christos
C
Profyris
Antonis
A
Nicolaou
Kristy
K
Boyle
Surindar S
SS
Cheema
Trevor J
TJ
Kilpatrick
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000166:cytology*; D001923:Brain Chemistry / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis*; D016923:Cell Death / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009836:Oligodendroglia / Q000378:metabolism*; D010641:Phenotype; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D013234:Stem Cells / Q000378:metabolism*; D016707:Tissue Fixation; D015854:Up-Regulation
D002352:Carrier Proteins; D002614:Chelating Agents; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D003471:Cuprizone