Demyelination and Remyelination in Anatomically Distinct Regions of the Corpus Callosum Following Cuprizone Intoxication

Neurosci Res. 2012 Jan;72(1):32-42. doi: 10.1016/j.neures.2011.10.002. Epub 2011 Oct 12.

Abstract

Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Spontaneous remyelination during early disease stages is thought to preserve and partially restore function. However, this process ceases in later stages despite the presence of pre-oligodendrocytes. Cuprizone-induced demyelination is a useful model with which to study the remyelination process. Previous studies have demonstrated heterogeneities in demyelination in individual animals. Here we investigated regional differences in demyelination and remyelination within the corpus callosum. C57BL/6 mice were fed 0.2% cuprizone for 5 weeks to induce demyelination. Remyelination was examined 2-5 weeks after cuprizone withdrawal. Immunohistochemistry and electron microscopy were used to quantify regional differences in demyelination, gliosis, and remyelination. We found that, while demyelination was limited in the rostral region of corpus callosum, nearly complete demyelination occurred in the caudal callosum, beginning at approximately -0.5mm from bregma. Astrogliosis and microgliosis were correlated with demyelination and differed between the rostral and caudal callosal structures. Remyelination upon cessation of cuprizone ensued at different rates with splenium remyelinating faster than dorsal hippocampal commissure. Our data show anatomical differences of cuprizone-induced demyelination and remyelination in the corpus callosum and the importance of examining specific callosal regions in myelin repair studies using this model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axons / pathology
  • Brain / physiopathology
  • Corpus Callosum / drug effects
  • Corpus Callosum / pathology*
  • Corpus Callosum / ultrastructure
  • Cuprizone
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / pathology*
  • Demyelinating Diseases / physiopathology
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein
  • Gliosis / chemically induced
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Myelin Sheath / drug effects*
  • Myelin Sheath / pathology*
  • Myelin Sheath / physiology
  • Nerve Tissue Proteins / drug effects
  • Nerve Tissue Proteins / metabolism
  • Oligodendroglia / drug effects
  • Weight Loss / drug effects

Substances

  • Glial Fibrillary Acidic Protein
  • Nerve Tissue Proteins
  • glial fibrillary astrocytic protein, mouse
  • Cuprizone