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Cobalamin (vitamin B(12)) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system.
- 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.)
- Subjects :
- Analysis of Variance
Animals
Central Nervous System pathology
Copper cerebrospinal fluid
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Gastrectomy adverse effects
Gene Expression Regulation physiology
Laparotomy adverse effects
Male
Nerve Fibers, Myelinated pathology
Rats
Rats, Sprague-Dawley
Time Factors
Tumor Necrosis Factor-alpha metabolism
Vitamin B 12 Deficiency etiology
Vitamin B 12 Deficiency metabolism
Central Nervous System metabolism
Copper metabolism
Prions genetics
Prions metabolism
RNA, Messenger metabolism
Vitamin B 12 metabolism
Vitamin B 12 Deficiency pathology
Subjects
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