VITAMIN B12 AND NORMAL PRIONS: TWO FIELDS APPARENTLY SO FAR, BUT IN REALITY SO NEAR

Abstract

Cobalamin (Cbl) deficiency causes an imbalance in some cytokines and growth factors in the central nervous system and peripheral nervous system of the rat, and in the serum and cerebrospinal fluid (CSF) of adult Cbl-deficient (Cbl-D) patients. We hypothesized that an imbalance in normal prion (PrPC) levels and/or synthesis might be involved in the pathogenesis of Cbl-D neuropathy. Using different appropriate enzyme-linked immunosorbent assays (ELISAs), we determined the levels of Cbl, tumour necrosis factor-a, epidermal growth factor, and PrPC in spinal cord (SC) and CSF of Cbl-D rats treated or not with different molecules; in serum, CSF from Cbl-D or multiple sclerosis (MS) patients; and in post-mortem SC samples taken from MS patients and control patients. We have demonstrated that: (i) Cbl deficiency induces excess PrPC regions (particularly octapeptide repeated (OR) region) in rat SC; (ii) the SC increase is mediated by a local Cbl deficiency-induced excess of tumour necrosis factor-a; and (iii) CSF and serum PrP^C concentrations in Cbl-D patients are significantly higher than in controls. CSF PrP^C concentrations are significantly lower in MS patients than neurological controls. The Cbl, EGF, and PrP^C levels were significantly decreased in post-mortem MS SCs in comparison with controls.