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The octapeptide repeat PrP C region and cobalamin‐deficient polyneuropathy of the rat
Author(s) -
Scalabrino Giuseppe,
Mutti Elena,
Veber Daniela,
Rodriguez Menendez Virginia,
Novembrino Cristina,
Calligaro Alberto,
Tredici Giovanni
Publication year - 2011
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.22225
Subject(s) - pathogenesis , myelin , polyneuropathy , sciatic nerve , medicine , cobalamin , endocrinology , tumor necrosis factor alpha , pathology , chemistry , central nervous system , vitamin b12
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. Muscle Nerve 2011