Continuous cuprizone intoxication allows active experimental autoimmune encephalomyelitis induction in C57BL/6 mice

Histochem Cell Biol. 2019 Aug;152(2):119-131. doi: 10.1007/s00418-019-01786-4. Epub 2019 Apr 23.

Abstract

Oligodendrocyte degeneration is a hallmark of multiple sclerosis pathology, and protecting oligodendrocytes and myelin is likely to be of clinical relevance. Traditionally, oligodendrocyte and myelin degeneration are viewed as a direct consequence of an inflammatory attack, but metabolic defects might be equally important. Appropriate animal models to study the interplay of inflammation and metabolic injury are, therefore, needed. Here, we describe that in spite of its immunosuppressive effects, a continuous intoxication with cuprizone allows the induction of active experimental autoimmune encephalomyelitis (EAE) by myelin oligodendrocyte glycoprotein (MOG35-55) immunization. Although the clinical severity of EAE is ameliorated in cuprizone-intoxicated mice, the recruitment of granulocytes, and especially, CD3+ lymphocytes into the forebrain is triggered by the cuprizone insult. Such combined lesions are further characterized by oligodendrocyte apoptosis and microglia activation, closely mimicking type III multiple sclerosis lesions. In summary, we provide a protocol that allows to study the direct interplay of immune-mediated and metabolic oligodendrocyte injury and its consequences for the cerebral white and grey matters.

Keywords: Multiple sclerosis; Neuroinflammation; Oligodendrocyte injury; Peripheral immune-cell recruitment.

MeSH terms

  • Administration, Oral
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • Cuprizone / administration & dosage
  • Cuprizone / toxicity*
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Oligodendroglia / drug effects
  • Oligodendroglia / immunology
  • Oligodendroglia / pathology
  • Peptide Fragments / immunology

Substances

  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-55)
  • Cuprizone