Accumulation of sulfatide in neuronal and glial cells of arylsulfatase A deficient mice

Abstract

Arylsulfatase A (ASA) degrades sulfatide, seminolipid and lactosylceramide sulfate, glycolipids recognized by the Sulph I antibody although sulfatide is considered the main antigen. Sulfatide is myelin associated but studies have shown a minor distribution also in non-myelin forming cells. The aim of this work was to further study sulfatide in neurons and astrocytes by immunohistochemistry, facilitated by investigation of tissue from adult ASA deficient (ASA -/-) mice. Cells with a low presence of sulfatide might be detected due to lack of ASA activity and accumulation of Sulph I antigens. Sulfatide positive astrocytes and neurons were more numerous and intensely stained in ASA -/- mice, demonstrating a sulfatide accumulation compared to controls. Sulph I staining was especially increased in the molecular layer of cerebellum, in which Purkinje cell dendrites displayed an altered morphology, and in layer IV-VI of cerebral cortex. In hippocampus, immunostaining was found in neuronal cytoplasm in ASA -/- but in nuclear membranes of control mice. We observed a gray matter astrogliosis, which appeared to be associated to sulfatide accumulation. In addition, the developmental change (<20 months) of Sulph I antigens, galactosylceramide, phospholipids and cholesterol were followed by lipid analyses which verified sulfatide and seminolipid accumulation in adult ASA -/- mice, although no lactosylceramide sulfate could be detected. In addition to demonstrating sulfatide in neurons and astrocytes, this study supports the value of ASA -/- mice as a model for metachromatic leukodystrophy and suggests that accumulation of sulfatide beyond myelin might contribute to the pathology of this disease.

Adult CST‐null mice maintain an increased number of oligodendrocytes

“…Since sulfatide is expressed in both astrocytes and oligodendrocytes (Pernber et al, 2002; Molander-Melin et al, 2004), these cell types are strong candidates for perturbation with sulfatide deficits. DAPI+/GFAP+ cells were abundant in the ventral columns of both the 15 day and 30 day old WT and sulfatide null mice; however, the number of DAPI+/GFAP+ cells did not differ between the 2 genotypes at either age (data not shown), indicating that the astrocyte population is not altered in the sulfatide null mice.…”

“…Although expressed by other cell types (Molander-Melin et al, 2004; Pernber et al, 2002), these lipids are highly enriched in oligodendrocyte membranes including the myelin sheath (Norton and Cammer, 1984). As a consequence of this early and abundant appearance, these lipids have been closely analyzed for possible roles in oligodendrocyte maturation and myelin formation (reviewed by Dupree and Popko, 1999).…”

Brain insulin resistance accelerates Aβ fibrillogenesis by inducing GM1 ganglioside clustering in the presynaptic membranes

“…GM1, which is a glycosphingolipid found in the outer layer of mammalian plasma membranes, is expressed abundantly on neuronal cell surfaces and plays important roles in differentiation, functioning and viability of cells, particularly neurons (Molander-Melin et al 2004;Yamamoto et al 2007). We previously reported that cell surface GM1 expression is strictly dependent on cell type, and that GM1 expression on the synaptic membrane is unique in terms of its ability to induce Ab fibril formation through GAb generation (Yamamoto et al 2007 and 2008).…”

Sulfatide with short fatty acid dominates in astrocytes and neurons

“…Biochemical analysis of grey matter sulfatide alone is thus hard to perform due to contamination of the myelin. However, the ASA mouse model has a high proportion of accumulated sulfatide in grey matter [9] and is therefore very suitable as a model system for grey matter sulfatide. ASA-⁄ -mice showed a marked increase in sulfatide C18 fatty acid at older ages.…”