Effects of Increased Sulfatide in Schwann and Mesenchymal Stromal Cells in Metachromatic Leukodystrophy

Abstract

Metachromatic leukodystrophy (MLD) is an inherited lysosomal storage disease caused by deficient arylsulfatase A (ARSA) activity, resulting in intra-lysosomal accumulation of sulfatide. Sulfatide is integral for proper maintenance of myelin in the central and peripheral nervous systems. This study characterized mitochondrial morphology, cytokine secretion and phagocytic activity in Schwann and mesenchymal cells isolated from ARSA-/- mice. Cells were treated with different, increasing concentrations of sulfatide for a period of 24 hours. ARSA-/- cells presented with persistent, increased fragmented mitochondrial structures suggestive of prolonged mitochondrial fission. Sulfatide treatments increased secretion of pro-inflammatory cytokines TNF-α and IL-1β in ARSA-/- cells. No differences were noted in the cellular phagocytic capacities following sulfatide treatment. These findings suggest that mitochondrial function is impacted. Further characterization of in vivo mitochondrial function in MLD tissues can provide a clearer pathological picture