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(C)s 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.