The octapeptide repeat PrPC 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 (PrPC) (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 PrPCs to normal rats to reproduce PNS Cbl-D-like lesions. We measured nerve PrPC 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. PrPC levels increased in Cbl-D nerves. The nerves of the PrPC-treated rats showed typical Cbl-D lesions, significantly decreased MNCV values, and significantly increased TNF-α levels. Discussion: OR-Abs prevent the myelin damage caused by increased OR-regions, and excess TNF-α is involved in the pathogenesis of Cbl-D polyneuropathy.