Low levels of cobalamin, epidermal growth factor, and normal prions in multiple sclerosis spinal cord

G. Scalabrino, D. Veber, R. De Giuseppe, F. Roncaroli

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 (PrPCs), 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 PrPC 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 PrPC 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 PrPC 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 PrPC 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 PrPCs may greatly hamper the remyelination process in MS patients, because they are key molecules of the machinery for remyelination.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalNeuroscience
Volume298
DOIs
Publication statusPublished - Jul 9 2015

Fingerprint

Prions
Vitamin B 12
Epidermal Growth Factor
Multiple Sclerosis
Spinal Cord
Cerebrospinal Fluid
Transcobalamins
Homocysteine
Tissue Banks
Myelin Sheath
Central Nervous System
Biomarkers
Enzyme-Linked Immunosorbent Assay

Keywords

  • Cobalamin
  • Epidermal growth factor
  • Holo-transcobalamin
  • Multiple sclerosis
  • Normal prions
  • Spinal cord

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Low levels of cobalamin, epidermal growth factor, and normal prions in multiple sclerosis spinal cord. / Scalabrino, G.; Veber, D.; De Giuseppe, R.; Roncaroli, F.

In: Neuroscience, Vol. 298, 09.07.2015, p. 293-301.

Research output: Contribution to journalArticle

Scalabrino, G. ; Veber, D. ; De Giuseppe, R. ; Roncaroli, F. / Low levels of cobalamin, epidermal growth factor, and normal prions in multiple sclerosis spinal cord. In: Neuroscience. 2015 ; Vol. 298. pp. 293-301.
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