Affected astrocytes in the spinal cord of the leukodystrophy vanishing white matter

Glia. 2018 Apr;66(4):862-873. doi: 10.1002/glia.23289. Epub 2017 Dec 29.


Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected. Astrocyte pathology starts postnatally in the sensory tracts, followed by changes in the astrocytic populations in the motor tracts. Studies in post-mortem tissue of two VWM patients, a 13-year-old boy and a 6-year-old girl, confirmed astrocyte abnormalities in the spinal cord. For proper development of new treatment options for VWM and, possibly, other leukodystrophies, future studies should investigate spinal cord involvement.

Keywords: astrocytes; leukoencephalopathy; neuroglia; neuropathology; spinal cord; vanishing white matter disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology*
  • Child
  • Disease Models, Animal
  • Eukaryotic Initiation Factor-2B / genetics
  • Eukaryotic Initiation Factor-2B / metabolism
  • Female
  • Gray Matter / embryology
  • Gray Matter / metabolism
  • Gray Matter / pathology
  • Humans
  • Immunohistochemistry
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / metabolism
  • Leukoencephalopathies / pathology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology*
  • White Matter / embryology
  • White Matter / metabolism
  • White Matter / pathology


  • Eukaryotic Initiation Factor-2B