p75NTR independent oligodendrocyte death in cuprizone-induced demyelination in C57BL/6 mice.
Feeding C57Bl/6 J mice the copper chelator cuprizone leads to selective apoptosis of mature oligodendrocytes and concomitant demyelination predominantly in the corpus callosum. The process of oligodendrocyte apoptosis in this animal model for multiple sclerosis (MS) involves early microglial activation, but no infiltration of T-lymphocytes. Therefore, this model could mimic early stages of oligodendrocyte degeneration Affected oligodendrocytes express the common neurotrophin receptor, p75(NTR), a 'stress-receptor' which under certain circumstances can induce apoptosis. Only affected oligodendrocytes in MS lesions and MS animal models express this receptor. In order to study the significance of p75(NTR) in the fate of oligodendrocytes, we have exposed wild-type as well as p75(NTR)-knockout mice to a 0.2% (w/w) cuprizone diet and performed a comparative immunohistochemical analysis of the corpus callosum at various time points. Surprisingly, our results show that the absence of p75(NTR) did not alter cuprizone-induced oligodendrocyte death (and subsequent de- or remyelination). Apparently, intracellular apoptosis pathways in adult oligodendrocytes do not require p75(NTR) activated signal transduction in the absence of T-lymphocytes and T-lymphocyte derived cytokines.
Copray
J C V M
JC
Department of Medical Physiology, University of Groningen, Groningen, the Netherlands. j.c.v.m.copray@med.rug.nl
Küst
B M
BM
Mantingh-Otter
I
I
Boddeke
H W G M
HW
D000818:Animals; D017209:Apoptosis; D003337:Corpus Callosum / Q000473:pathology; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008996:Monoamine Oxidase Inhibitors; D009416:Nerve Regeneration; D009836:Oligodendroglia / Q000473:pathology*; D020800:Receptor, Nerve Growth Factor / Q000235:genetics*; D013601:T-Lymphocytes / Q000473:pathology
D008996:Monoamine Oxidase Inhibitors; D020800:Receptor, Nerve Growth Factor; D003471:Cuprizone