Myelin abnormalities in the optic and sciatic nerves in mice with GM1-gangliosidosis

ASN Neuro. 2015 Feb 18;7(1):1759091415568913. doi: 10.1177/1759091415568913. Print 2015 Jan-Feb.

Abstract

GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old β-galactosidase (β-gal) +/? and β-gal -/- mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the β-gal -/- mice than in unaffected β-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the β-gal -/- mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of β-gal -/- mice than in β-gal +/? mice; however, cholesteryl esters were enriched in the β-gal -/- mice. No major abnormalities in these lipids were detected in the sciatic nerve of the β-gal -/- mice. The abnormalities in GM1 and myelin lipids in optic nerve of β-gal -/- mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and β-gal -/- mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of β-gal -/- mice is likely due to the greater glycolipid storage in optic nerve.

Keywords: X-ray diffraction; cerebrosides; gangliosides; lipids.

Publication types

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

MeSH terms

  • Animals
  • Chromatography, Thin Layer
  • Densitometry
  • Gangliosidosis, GM1 / genetics*
  • Gangliosidosis, GM1 / pathology*
  • Genotype
  • Lipid Metabolism / genetics
  • Mice
  • Mice, Transgenic
  • Myelin Sheath / metabolism
  • Myelin Sheath / pathology*
  • Optic Nerve / cytology*
  • Optic Nerve / pathology*
  • Sciatic Nerve / pathology*
  • X-Ray Diffraction
  • beta-Galactosidase / deficiency*
  • beta-Galactosidase / genetics

Substances

  • beta-Galactosidase