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.
Cobalamin (vitamin B12) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system / G. Scalabrino, D. Veber, E. Mutti, A. Calligaro, S. Milani, G. Tredici. - In: EXPERIMENTAL NEUROLOGY. - ISSN 0014-4886. - 233:1(2012), pp. 380-390.
|Titolo:||Cobalamin (vitamin B12) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system|
|Parole Chiave:||Cerebrospinal fluid; Cobalamin deficiency; Epidermal growth factor; Normal prion protein; Octapeptide repeat region; Spinal cord; Tumor necrosis factor-α|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.expneurol.2011.11.003|
|Appare nelle tipologie:||01 - Articolo su periodico|