Sulfatide is essential for the maintenance of CNS myelin and axon structure

Abstract

Galactocerebroside (GalC) and sulfatide are abundant myelin lipids. In mice incapable of synthesizing these lipids, myelin is thin and regionally unstable and exhibits several subtle structural abnormalities. Although galactolipid-null mice have been beneficial in the analysis of galactolipid function, it has not been possible to differentiate between the functions of GalC and sulfatide with these mice alone. In the present work, we have analyzed a murine model that forms normal levels of GalC but is incapable of synthesizing sulfatide. By comparing a plethora of morphological features between the galactolipid-null and the sulfatide-null mice, we have begun to differentiate between the specific functions of these closely related lipids. The most striking difference between these two mutants is the reduction of myelin developmental abnormalities (e.g., redundant and uncompacted myelin sheaths) in young adult sulfatide-null mice as compared with the galactolipid-null animals. Although sulfatide appears to play a limited role in myelin development, this lipid is essential for myelin maintenance, as the prevalence of redundant, uncompacted, and degenerating myelin sheaths as well as deteriorating nodal/paranodal structure is increased significantly in aged sulfatide-null mice as compared with littermate wildtype mice. Finally, we show that the role played by sulfatide in CNS maintenance is not limited to the myelin sheath, as axonal caliber and circularity are normal in young adult mutant mice but are significantly altered in aged sulfatide-null animals.

Disruption of axo–glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons

“…Similar phenotypes were observed at the paranodes in CGT mutants (18,19). CGT encodes an enzyme that is needed for the biosynthesis of two important myelin lipids, galactocerebroside and sulfatide (10,(18)(19)(20)(21). Using subcellular fractionation of NF155 in detergents, Rasband and coworkers (22) proposed a model in which myelin lipids assemble in stable lipid rafts to stabilize the clustering of NF155 at the glial side of AGJs.…”

Encephalopathy Caused by Ablation of Very Long Acyl Chain Ceramide Synthesis May Be Largely Due to Reduced Galactosylceramide Levels

“…Astrogliosis is sometimes seen in white matter deficiencies and has been observed in cerebroside sulfotransferase-null and in galactosylceramidase-null (twitcher) mice (54,55). However, the brain disease in the CerS2-null mouse does not affect solely white matter regions.…”

Neurolipidomics: challenges and developments

“…Piomelli has recently outlined the involvement of four lipid signaling pathways in the nervous system from neocortex to the processing of behavior (14). The enrichment of sphingolipids in myelin sheath relative to other locations in the nervous system and other systems indicates the involvement of these specific lipids in myelin packing and function which have been investigated through different animal models (25)(26)(27). Despite the enrichment of plasmalogen in the neurolipidome, a clear relationship between the abundance of plasmalogen and its role in the nervous system remains to be determined (28).…”