title: The octapeptide repeat PrP(C) region and cobalamin-deficient polyneuropathy of the rat.
abstract: BACKGROUND
  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.
authors.affiliation: Città Studi Department, Laboratory of Neuropathology, University of Milan, Milan, Italy. giuseppe.scalabrino@unimi.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scalabrino
authors.forename: Elena
authors.initials: E
authors.lastname: Mutti
authors.forename: Daniela
authors.initials: D
authors.lastname: Veber
authors.forename: Virginia
authors.initials: V
authors.lastname: Rodriguez Menendez
authors.forename: Cristina
authors.initials: C
authors.lastname: Novembrino
authors.forename: Alberto
authors.initials: A
authors.lastname: Calligaro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tredici
mesh_terms: D000818:Animals; D051379:Mice; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000633:toxicity*; D011115:Polyneuropathies / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018621:PrPC Proteins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014805:Vitamin B 12 / Q000378:metabolism / Q000633:toxicity*
chemical_list: D009842:Oligopeptides; D018621:PrPC Proteins; D014409:Tumor Necrosis Factor-alpha; D014805:Vitamin B 12