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Cobalamin (vitamin B(12)) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system.

Authors :
Scalabrino G
Veber D
Mutti E
Calligaro A
Milani S
Tredici G
Source :
Experimental neurology [Exp Neurol] 2012 Jan; Vol. 233 (1), pp. 380-90. Date of Electronic Publication: 2011 Nov 12.
Publication Year :
2012

Abstract

The pathogenesis of cobalamin (Cbl)-deficient (Cbl-D) neuropathy is not clear, nor is the role of prions (PrP(C)) in myelin maintenance. However, as it is known that Cbl deficiency damages myelin by increasing tumor necrosis factor (TNF)-α and decreasing epidermal growth factor (EGF) levels in rat spinal cord (SC), and that TNF-α and EGF regulate PrP(C) expression in vitro, we investigated whether Cbl deficiency modifies SC PrP(C) and PrP(C)-mRNA levels in Cbl-D rats. PrP(C) levels had increased by the time myelin lesions appeared. This increase was mediated by excess myelinotoxic TNF-α and prevented by EGF, which proved to be as effective as Cbl in preventing Cbl deficiency-induced lesions. There were no significant changes in hepatic PrP(C) levels of Cbl-D rats. Anti-octapeptide repeat (OR) region antibodies normalized SC myelin morphology. Cbl deficiency greatly reduced SC PrP(C)-mRNA levels, which were subsequently increased by Cbl and EGF. Cbl deficiency-induced excess OR is myelin-damaging, but new PrP(C) synthesis is a common effect of different myelinotrophic agents.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1090-2430
Volume :
233
Issue :
1
Database :
MEDLINE
Journal :
Experimental neurology
Publication Type :
Academic Journal
Accession number :
22116041
Full Text :
https://doi.org/10.1016/j.expneurol.2011.11.003