title: Cobalamin (vitamin B(12)) regulation of PrP(C), PrP(C)-mRNA and copper levels in rat central nervous system.
abstract: The pathogenesis of cobalamin (Cbl)-deficient (Cbl-D) neuropathy is not clear, nor is the role of prions (PrP(C)) in myelin maintenance. However, as it is known that Cbl deficiency damages myelin by increasing tumor necrosis factor (TNF)-α and decreasing epidermal growth factor (EGF) levels in rat spinal cord (SC), and that TNF-α and EGF regulate PrP(C) expression in vitro, we investigated whether Cbl deficiency modifies SC PrP(C) and PrP(C)-mRNA levels in Cbl-D rats. PrP(C) levels had increased by the time myelin lesions appeared. This increase was mediated by excess myelinotoxic TNF-α and prevented by EGF, which proved to be as effective as Cbl in preventing Cbl deficiency-induced lesions. There were no significant changes in hepatic PrP(C) levels of Cbl-D rats. Anti-octapeptide repeat (OR) region antibodies normalized SC myelin morphology. Cbl deficiency greatly reduced SC PrP(C)-mRNA levels, which were subsequently increased by Cbl and EGF. Cbl deficiency-induced excess OR is myelin-damaging, but new PrP(C) synthesis is a common effect of different myelinotrophic agents.
authors: Città Studi Department, Laboratory of Neuropathology, University of Milan, 20133 Milan, Italy. giuseppe.scalabrino@unimi.it
authors: Giuseppe
authors: G
authors: Scalabrino
authors: Daniela
authors: D
authors: Veber
authors: Elena
authors: E
authors: Mutti
authors: Alberto
authors: A
authors: Calligaro
authors: Silvano
authors: S
authors: Milani
authors: Giovanni
authors: G
authors: Tredici
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D003300:Copper / Q000134:cerebrospinal fluid / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005743:Gastrectomy / Q000009:adverse effects; D005786:Gene Expression Regulation / Q000502:physiology; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D011328:Prions / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D011328:Prions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003300:Copper; D014805:Vitamin B 12