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

Abstract

GM1 gangliosidosis is a glycosphingolipid lysosomal storage disease caused by a genetic deficiency of acid b-galactosidase (β-gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Less information is available on the neurochemical pathology in optic nerve and sciatic nerve of GM1- gangliosidosis. Here we analyzed the lipid content and myelin structure in optic and sciatic nerve in 7 and 10 month old normal β-gal (+/?) and GM1-gangliosidosis β-gal (-/-) mice. Optic nerve weight was lower in the β-gal -/- mice than in unaffected β-gal +/? mice, but no difference was seen between the normal and the β-gal -/- mice for sciatic nerve weight. The concentrations of GM1 and GA1 were significantly higher in optic nerve and sciatic nerve in the β-gal -/- mice than in β-gal +/? mice. The content and composition of myelin-enriched cerebrosides, sulfatides, plasmalogen ethanolamines were 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 significant abnormalities in these myelin enriched lipids were detected in sciatic nerve of the β-gal -/- mice. The abnormalities in GM1 and myelin lipids in optic nerve of β-gal -/- mice were also associated with abnormalities in the X-ray diffraction pattern including myelin content in fresh nerves [M/(M +B)] and periodicity (d). With the exception of a slight reduction in myelin content, no abnormalities in the X-ray diffraction pattern were observed in sciatic nerve of β-gal -/- mice. The results indicate that neurochemical pathology is greater in optic nerve than in sciatic nerve of β-gal -/- mice.