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Licensed Unlicensed Requires Authentication Published by De Gruyter November 21, 2012

Normal prions as a new target of cobalamin (vitamin B12) in rat central nervous system

  • Giuseppe Scalabrino EMAIL logo and Daniela Veber

Abstract

The pathogenesis of cobalamin (Cbl)-deficient (Cbl-D) neuropathy and the role of normal prions (PrPcs) in myelin maintenance are both subjects of debate. We have demonstrated that Cbl deficiency damages myelin by increasing tumor necrosis factor (TNF)-α, and decreasing epidermal growth factor (EGF) levels in the rat central nervous system (CNS). It is known that TNF-α and EGF regulate PrPc expression in vitro, and that myelin vacuolation, reactive astrocytosis and microglial activation are common to rat Cbl-D neuropathy and some prion diseases. We have shown that Cbl deficiency leads to high levels of PrPcs [particularly the octapeptide repeat (OR) domains] in the rat CNS thereby damaging the spinal cord (SC) myelin, and that chronic intra-cerebroventricular treatment with anti-OR antibodies normalizes SC myelin morphology. We have also found that PrPc levels are increased in the SC of Cbl-D rats by the time the myelin lesions appear, and that this increase is mediated by excess myelinotoxic TNF-α and prevented by EGF treatment, which has proved to be as effective as Cbl in preventing Cbl deficiency-induced lesions. Cbl stimulates PrPc mRNA-related synthesis in Cbl-D SC and duodenum, two rat tissues that are severely affected by Cbl deficiency. New PrPc synthesis is a common effect of various myelinotrophic agents, two of which (EGF and anti-TNF-α antibodies) also stimulate PrPc mRNA-related synthesis in the SC of Cbl-D rats.


Corresponding author: Giuseppe Scalabrino, Laboratory of Neuropathology, ‘Città Studi’ Department, University of Milan, via Mangiagalli 31, 20133 Milan, Italy, Phone: +39 02 50315348, Fax: +39 02 50315338

We gratefully acknowledge the editorial assistance of Dr. T. Cerchiaro, Laboratory of Neuropathology, ‘Città Studi’ Department, University of Milan, Milan, Italy.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2012-7-23
Accepted: 2012-10-24
Published Online: 2012-11-21
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

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