The octapeptide repeat PrP(C) region and cobalamin-deficient polyneuropathy of the rat

Introduction: Cobalamin (Cbl) deficiency affects the peripheral nervous system (PNS) morphologically and functionally. We investigated whether the octapeptide repeat (OR) region of prion protein (PrP^C) (which is claimed to have myelinotrophic properties) is involved in the pathogenesis of rat Cbl‐deficient (Cbl‐D) polyneuropathy. Methods: We intracerebroventricularly administered antibodies (Abs) against the OR region (OR‐Abs) to Cbl‐D rats to prevent myelin damage and maximum nerve conduction velocity (MNCV) abnormalities, and PrP^Cs to normal rats to reproduce PNS Cbl‐D–like lesions. We measured nerve PrP^C levels and MNCV. Results: The OR‐Abs normalized myelin ultrastructure, MNCV values, and tumor necrosis factor (TNF)‐α levels in the sciatic and tibial nerves of Cbl‐D rats. PrP^C levels increased in Cbl‐D nerves. The nerves of the PrP^C‐treated rats showed typical Cbl‐D lesions, significantly decreased MNCV values, and significantly increased TNF‐α levels. Conclusions: OR‐Abs prevent the myelin damage caused by increased OR regions, and excess TNF‐α is involved in the pathogenesis of Cbl‐D polyneuropathy. Muscle Nerve 2011