Low levels of cobalamin, epidermal growth factor, and normal prions in multiple sclerosis spinal cord. (9th July 2015)

• Record Type: Journal Article
• Authors: Scalabrino, G.; Veber, D.; De Giuseppe, R.; Roncaroli, F.
• Is Part Of: Neuroscience. Volume 298(2015)
• Page Start: 293
• Page End: 301
• Publication Date: 2015-07-09
• Subjects: Abs antibodies -- AIA automated immunoassay analyzer -- Cbl cobalamin -- Cbl-D Cbl-deficient -- CNS central nervous system -- CSF cerebrospinal fluid -- EGF epidermal growth factor -- ELISA enzyme-linked immunosorbent assay -- holo-TC holotranscobalamin -- LFB Luxol Fast Blue -- MHC major histocompatibility complex -- MOG myelin oligodendrocyte glycoprotein -- MS multiple sclerosis -- ODC oligodendrocyte -- ORO Oil Red O -- PK proteinase K -- PP primary-progressive -- PrPC normal cellular prion -- PrPSC PrP scrapie -- r.p.m. revolutions per minute -- RR relapsing-remitting -- SC spinal cord -- SP secondary-progressive -- tHCYS total homocysteine; cobalamin -- epidermal growth factor -- holo-transcobalamin -- multiple sclerosis -- normal prions -- spinal cord; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.04.020
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Multiple sclerosis (MS) spinal cords (SCs) are deficient in cobalamin. Epidermal growth factor (EGF) and normal prion (PrP C ) levels are decreased in MS SC. SC EGF and PrP C levels paralleled those found in the MS cerebrospinal fluid (CSF). Abstract: We have previously demonstrated that multiple sclerosis (MS) patients have abnormal cerebrospinal fluid (CSF) levels of the key myelin-related molecules cobalamin (Cbl), epidermal growth factor (EGF), and normal cellular prions (PrP C s), thus confirming that some CSF abnormalities may be co-responsible for remyelination failure. We determined the levels of these three molecules in post-mortem spinal cord (SC) samples taken from MS patients and control patients. The control SC samples, almost all of which came from non-neurological patients, did not show any microscopic lesions of any type. All of the samples were supplied by the U.K. MS Tissue Bank. The Cbl, EGF, and PrP C levels were determined using enzyme-linked immunosorbent assays. The SC total homocysteine level was determined using a competitive immunoenzymatic assay. CSF samples, taken from a further group of MS patients, were used for the assay of holo-transcobalamin (holo-TC) levels. The Cbl, EGF, and PrP C levels were significantly decreased in MS SCs in comparison with controls and, paradoxically, the decreased Cbl levels were associated with decreased SC levels of homocysteine, a biochemical marker of Cbl deficiency. The trends of EGF and PrP C levels paralleled those previously found in CSF, whereas that of Cbl was the opposite. There was no significant difference in CSF holo-TC levels between the MS patients and the controls. Given that we have previously demonstrated that Cbl positively regulates central nervous system EGF levels, it is conceivable that the low EGF levels in the MS SC may be causally related to a local decrease in Cbl levels. Only PrP C levels were invariably decreased in both the SC and CSF regardless of the clinical course of the disease. These findings suggest that the simultaneous lack of Cbl, EGF, and PrP C s may greatly hamper the remyelination process in MS patients, because they are key molecules of the machinery for remyelination.