Oligodendroglial impact on axonal function and survival - a hypothesis

Curr Opin Neurol. 2008 Jun;21(3):235-41. doi: 10.1097/WCO.0b013e328300c71f.

Abstract

Purpose of review: Although multiple sclerosis is considered the prototype of a primary autoimmune disease in the central nervous system, there is emerging evidence that primary oligodendrocyte dysfunctions can suffice to trigger a secondary immune response in the nervous system. This short review focuses on the possible primary role of oligodendrocytes in axon loss and inflammatory demyelination.

Recent findings: The analysis of natural and engineered mouse mutants has provided unexpected insight into oligodendrocyte function beyond that of axonal myelination for rapid impulse propagation. Specifically, mutations in some genes thought to be required for myelin assembly revealed an additional role of oligodendrocytes in supporting long-term axonal function and survival. Other mutations have been reported that cause both central nervous system demyelination and neuroinflammation, with pathological features known from human leukodystrophy patients. In human multiple sclerosis, demyelination leads invariably to axon loss, but the underling pathomechanisms may not be restricted to that of a primary immune-mediated disorder.

Summary: Collectively, experimental and pathological findings point to a primary role of myelinating glia in long-term axonal support and suggest that defects of lipid metabolism in oligodendrocytes contribute to inflammatory myelin diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Axons / immunology*
  • Axons / physiology
  • Cell Survival / immunology
  • Demyelinating Diseases / immunology*
  • Eicosanoids / immunology
  • Humans
  • Mice
  • Mice, Neurologic Mutants
  • Myelin Sheath / immunology
  • Myelin Sheath / physiology
  • Nerve Fibers, Myelinated / immunology*
  • Oligodendroglia / immunology*
  • Oligodendroglia / physiology
  • Peroxisomes / physiology*

Substances

  • Eicosanoids