Proteolipid protein gene expression in demyelination and remyelination of the central nervous system: A model for multiple sclerosis

Moses Rodriguez, Naraporn Prayoonwiwat, Charles Howe, Kathleen Sanborn

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

We asked whether nonlethal injury to the oligodendrocyte as manifested by altered myelin gene expression is an early event in the pathogenesis of demyelinating disease and subsequent remyelination. Using simultaneous in situ hybridization and immunocytochemistry, we studied expression of proteolipid protein (PLP) antigen and mRNA in spinal cords of normal adult mice and of mice infected with Theiler’s virus which provides an excellent model for multiple sclerosis. Downregulation of PLP mRNA was observed within 3 days and persisted for as long as 367 days following intracerebral virus infection of SJL/J mice which are susceptible to chronic demyelination. Downregulation of myelin gene products preceded the development of prominent inflammation and demyelination observed following virus infection. In contrast, no change from control uninfected mice was observed in the expression of PLP mRNA following infection of C57BL/10SNJ mice which are resistant to demyelination. Treatment of chronically infected susceptible SJL/J mice with a regimen which promotes CNS-type (oligodendroglial) remyelination resulted in a 3- to 4-fold increase in PLP mRNA expression in oligodendrocytes. Actin mRNA expression in PLP antigen-positive cells was unchanged following TMEV-induced demyelination or remyelination indicating up- or downregulation of myelin gene products as compared to constitutively expressed actin gene. These experiments support the hypothesis that early regulation of myelin gene expression may be an important determinant in demyelination and in remyelination following nonlethal injury to oligodendrocytes.

Original languageEnglish (US)
Pages (from-to)136-143
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume53
Issue number2
DOIs
StatePublished - Mar 1994

Keywords

  • Glia
  • Multiple sclerosis
  • Myelin
  • Oligodendrocyte
  • Picornavirus
  • TMEV
  • Theiler’s virus

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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