Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

C. Espejo, J. Carrasco, J. Hidalgo, M. Penkowa, A. Garcia, I. Sáez-Torres, E. M. Martínez-Cáceres

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43 Citations (Scopus)


Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-γ, a pro-inflammatory cytokine, in the control of metallothioneins expression during experimental autoimmune encephalomyelitis in interferon-γ receptor knockout mice with two different genetic backgrounds: 129/Sv and C57BL/6x129/Sv. Mice with experimental autoimmune encephalomyelitis showed a significant induction of metallothioneins-I+II in the spinal cord white matter, and to a lower extent in the brain. Interferon-γ receptor knockout mice suffered from a more severe experimental autoimmune encephalomyelitis, and interestingly showed a higher metallothioneins-I+II induction in both white and grey matter of the spinal cord and in the brain. In contrast to the metallothioneins-I+II isoforms, metallothionein-III expression remained essentially unaltered during experimental autoimmune encephalomyelitis; interferon-γ receptor knockout mice showed an altered metallothionein-III expression (a slight increase in the spinal cord white matter) only in the C57BL/6x129/Sv background. Metallothioneins-I+II proteins were prominent in areas of induced cellular infiltrates. Reactive astrocytes and activated monocytes/macrophages were the sources of metallothioneins-I+II proteins. From these results we suggest that metallothioneins-I+II but not metallothionein-III may play an important role during experimental autoimmune encephalomyelitis, and indicate that the pro-inflammatory cytokine interferon-γ is unlikely an important factor in this response. © 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)1055-1065
Publication statusPublished - 22 Aug 2001


  • Antioxidant proteins
  • Interferon γ
  • Multiple sclerosis
  • Neuroprotein
  • Oxidative stress


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