Distribution of C16:0, C18:0, C24:1, and C24:0 sulfatides in central nervous system lipid rafts by quantitative ultra-high-pressure liquid chromatography tandem mass spectrometry.

Sulfated galactosylceramides (sulfatides) are glycosphingolipids associated with cholesterol- and sphingolipid-enriched membrane microdomains (lipid rafts) and are highly expressed in brain tissue. Although it is known that sulfatide species show heterogeneity in their fatty acid acyl group composition throughout brain development, their lipid raft distribution and biological relevance is poorly understood. We validated a fast and sensitive ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to measure developmentally regulated sulfatide species (C16:0, C18:0, C24:1, and C24:0) in central nervous system (CNS) lipid rafts isolated without using detergent.

Axonopathy is a compounding factor in the pathogenesis of Krabbe disease.

Loss-of-function of the lysosomal enzyme galactosyl-ceramidase causes the accumulation of the lipid raft-associated sphingolipid psychosine, the disruption of postnatal myelination, neurodegeneration and early death in most cases of infantile Krabbe disease. This work presents a first study towards understanding the progression of axonal defects in this disease using the Twitcher mutant mouse. Axonal swellings were detected in axons within the mutant spinal cord as early as 1 week after birth.

Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a mouse model of Krabbe disease.

Lysosomal beta-galactosylceramidase deficiency results in demyelination and inflammation in the nervous system causing the neurological Krabbe disease. In the Twitcher mouse model of this disease, we found that neurological symptoms parallel progressive and severe lymphopenia. Although lymphopoiesis is normal before disease onset, primary and secondary lymphoid organs progressively degenerate afterward.