Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis

Giuseppe Scalabrino, Daniela Galimberti, Elena Mutti, Diego Scalabrini, Daniela Veber, Milena De Riz, Fabrizia Bamonti, Elisabetta Capello, Giovanni Luigi Mancardi, Elio Scarpini

Research output: Contribution to journalArticle

Abstract

We investigated whether the physiological regulation of cerebrospinal fluid (CSF) levels of tumor necrosis factor (TNF)-α, epidermal growth factor (EGF), and nerve growth factor (NGF) by cobalamin (Cbl) that is observed in rat and human central nervous system (CNS) is retained in the CSF of patients with multiple sclerosis (MS). The study involved 158 MS patients grouped on the basis of the different clinical courses (relapsing-remitting (RR), secondary-progressive (SP), and primary-progressive (PP)), and 76 gender- and age-matched control patients with other non-inflammatory and non-neoplastic neurological diseases. The MS patients were therapy-free at the time of lumbar puncture. CSF Cbl and EGF were blindly measured by means of radioimmunoassays, and CSF TNF-α, and NGF by means of highly sensitive enzyme-linked immunosorbent assays. Serum EGF was also measured in 38 of the MS patients and 20 healthy controls. CSF Cbl levels were significantly higher (RR patients 27.9 ± 9.7 pg/ml, p <0.0001 vs. C; SP patients 25.4 ± 8 pg/ml, p <0.02 vs. C), and CSF TNF-α and EGF levels significantly lower in the patients with the RR (TNF-α 28.3 ± 23.4 × 10 -3 pg/ml, p <0.0001 vs. C; EGF 129.9 ± 44.8 pg/ml, p <0.02 vs. C) or SP (TNF-α 20.5 ± 20.5 × 10 -3 pg/ml, p <0.001 vs. C; EGF 116.5 ± 24.8 pg/ml, p <0.05 vs. C) clinical course than in controls (Cbl 21 ± 4.6 pg/ml; TNF-α 75.6 ± 34.7 × 10 -3 pg/ml; EGF 170.2 ± 54.8 pg/ml). There were no differences in CSF NGF or serum EGF levels between any of the MS clinical courses and controls. Our results indicate that: (a) the positive Cbl-mediated regulation of myelino- and oligodendrocyte-trophic EGF is lost in the CSF of RR- or SP-MS patients; (b) the decrease in EGF levels in the CSF may be one factor impeding CNS remyelination in MS; and (c) the PP clinical course may have different pathogenetic mechanism(s) also on the basis of the molecules investigated in this study.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalBrain Research
Volume1333
DOIs
Publication statusPublished - May 28 2010

Keywords

  • Cerebrospinal fluid
  • Cobalamin
  • Epidermal growth factor
  • Multiple sclerosis
  • Nerve growth factor
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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  • Cite this

    Scalabrino, G., Galimberti, D., Mutti, E., Scalabrini, D., Veber, D., De Riz, M., Bamonti, F., Capello, E., Mancardi, G. L., & Scarpini, E. (2010). Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis. Brain Research, 1333, 64-71. https://doi.org/10.1016/j.brainres.2010.03.073