Regional differences between grey and white matter in cuprizone induced demyelination

Brain Res. 2009 Aug 4;1283:127-38. doi: 10.1016/j.brainres.2009.06.005. Epub 2009 Jun 12.

Abstract

Cuprizone feeding is a commonly used model to study experimental de- and remyelination, with the corpus callosum being the most frequently investigated white matter tract. We have previously shown that demyelination is also extensive in the cerebral cortex in the cuprizone model. In the current study, we have performed a detailed analysis of the dynamics of demyelination in the cortex in comparison to the corpus callosum. Prominent and almost complete demyelination in the corpus callosum was observed after 4.5-5 weeks of 0.2% cuprizone feeding, whereas complete cortical demyelination was only observed after 6 weeks of cuprizone feeding. Interestingly, remyelination in the corpus callosum occurred even before the termination of cuprizone administration. Accumulation of microglia in the corpus callosum started as early as week 3 reaching its maximum at week 4.5 and was still significantly elevated at week 6 of cuprizone treatment. Within the cortex only a few scattered activated microglial cells were found. Furthermore, the intensity of astrogliosis, accumulation of oligodendrocyte progenitor cells and nestin positive cells differed between the two areas investigated. The time course and dynamics of demyelination differ in the corpus callosum and in the cortex, suggesting different underlying pathomechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Brain / drug effects
  • Brain / pathology*
  • Brain / physiopathology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Chelating Agents / toxicity
  • Corpus Callosum / drug effects
  • Corpus Callosum / pathology
  • Corpus Callosum / physiopathology
  • Cuprizone / toxicity
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / pathology*
  • Demyelinating Diseases / physiopathology
  • Disease Models, Animal
  • Disease Progression
  • Gliosis / chemically induced
  • Gliosis / pathology
  • Gliosis / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / pathology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Nerve Fibers, Myelinated / drug effects
  • Nerve Fibers, Myelinated / pathology*
  • Nerve Regeneration / physiology
  • Neurotoxins / toxicity
  • Oligodendroglia / drug effects
  • Oligodendroglia / pathology
  • Stem Cells / drug effects
  • Stem Cells / pathology
  • Time Factors

Substances

  • Chelating Agents
  • Neurotoxins
  • Cuprizone