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

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.

• Authors: Karie A Heinecke, Adrienne Luoma, Alessandra d'Azzo, Daniel A Kirschner, Thomas N Seyfried
• Journal: ASN neuro (ASN Neuro) 2015 Jan-Feb Vol. 7 Issue 1 ISSN: 1759-0914 [Electronic] United States
• PMID: 25694553 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2015.

Chemical References

• beta-Galactosidase

Topics

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