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EnglishAbstract The pathogenesis of cobalamin (Cbl)-deficient (Cbl-D) neuropathy and the role of normal prions (PrPcs) in myelin maintenance are both subjects of debate. We have demonstrated that Cbl deficiency damages myelin by increasing tumor necrosis factor (TNF)-α, and decreasing epidermal growth factor (EGF) levels in the rat central nervous system (CNS). It is known that TNF-α and EGF regulate PrPc expression in vitro, and that myelin vacuolation, reactive astrocytosis and microglial activation are common to rat Cbl-D neuropathy and some prion diseases. We have shown that Cbl deficiency leads to high levels of PrPcs [particularly the octapeptide repeat (OR) domains] in the rat CNS thereby damaging the spinal cord (SC) myelin, and that chronic intra-cerebroventricular treatment with anti-OR antibodies normalizes SC myelin morphology. We have also found that PrPc levels are increased in the SC of Cbl-D rats by the time the myelin lesions appear, and that this increase is mediated by excess myelinotoxic TNF-α and prevented by EGF treatment, which has proved to be as effective as Cbl in preventing Cbl deficiency-induced lesions. Cbl stimulates PrPc mRNA-related synthesis in Cbl-D SC and duodenum, two rat tissues that are severely affected by Cbl deficiency. New PrPc synthesis is a common effect of various myelinotrophic agents, two of which (EGF and anti-TNF-α antibodies) also stimulate PrPc mRNA-related synthesis in the SC of Cbl-D rats.
Normal prions as a new target of cobalamin (vitamin B 12) in rat central nervous system / G. Scalabrino, D. Veber. - In: CLINICAL CHEMISTRY AND LABORATORY MEDICINE. - ISSN 1434-6621. - 51:3(2013 Mar), pp. 601-606.
| Titolo: | Normal prions as a new target of cobalamin (vitamin B 12) in rat central nervous system | |
| Autori: | SCALABRINO, GIUSEPPE (Primo) VEBER, DANIELA (Ultimo) | |
| Parole Chiave: | Cerebrospinal fluid; Cobalamin deficiency; Epidermal growth factor; Normal prion protein; Spinal cord; Tumor necrosis factor-α | |
| Settore Scientifico Disciplinare: | Settore MED/04 - Patologia Generale | |
| Data di pubblicazione: | mar-2013 | |
| Rivista: | ||
| Tipologia: | Article (author) | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1515/cclm-2012-0474 | |
| Appare nelle tipologie: | 01 - Articolo su periodico |
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