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.

Scalabrino, G., Veber, D., Mutti, E., Calligaro, A., Milani, S., Tredici, G. (2012). Cobalamin (vitamin B(12)) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system. EXPERIMENTAL NEUROLOGY, 233(1), 380-390 [10.1016/j.expneurol.2011.11.003].

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

TREDICI, GIOVANNI
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.
Articolo in rivista - Articolo scientifico
Nerve Fibers, Myelinated; Animals; Laparotomy; Tumor Necrosis Factor-alpha; Analysis of Variance; Vitamin B 12 Deficiency; Vitamin B 12; Disease Models, Animal; Copper; Central Nervous System; Prions; Rats; RNA, Messenger; Rats, Sprague-Dawley; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Gastrectomy; Time Factors; Male
English
12-nov-2011
2012
233
1
380
390
none
Scalabrino, G., Veber, D., Mutti, E., Calligaro, A., Milani, S., Tredici, G. (2012). Cobalamin (vitamin B(12)) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system. EXPERIMENTAL NEUROLOGY, 233(1), 380-390 [10.1016/j.expneurol.2011.11.003].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/45723
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