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

Clin Chem Lab Med. 2013 Mar 1;51(3):601-6. doi: 10.1515/cclm-2012-0474.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Copper / cerebrospinal fluid
  • Epidermal Growth Factor / metabolism
  • Prions / metabolism*
  • Rats
  • Spinal Cord / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamin B 12 / metabolism*
  • Vitamin B 12 Deficiency / metabolism
  • Vitamin B 12 Deficiency / pathology


  • Prions
  • Tumor Necrosis Factor-alpha
  • Epidermal Growth Factor
  • Copper
  • Vitamin B 12