Changes in the Metabolism of Sphingomyelin and Ceramide in the Brain Structures and Spinal Cord of Transgenic Mice (FUS(1-359)) Modeling Amyotrophic Lateral Sclerosis

Changes in the expression of genes for enzymes of sphingolipid metabolism in transgenic FUS mice (FUS (1-359)) simulating amyotrophic lateral sclerosis (ALS) were found. The profiles of molecular species of sphingomyelins (SM) and ceramides (CER) in the structure of the brain and in the spinal cord were analyzed. During the development of ALS, changes in the spectrum of molecular types of CER were noted only in the spinal cord, where almost all CER decreased in relation to the control after two and three months of the course of the disease. After four months of the development of the pathology, an increase in the expression of the acid ceramidase gene was observed, as a result of which sphingosine can be formed, which has pronounced proapoptotic properties. Analysis of gene expression of CER and galactosylceramide (GalCER) metabolism enzymes indicates the possibility of GalCER functioning as a source for maintaining CER levels at the terminal stage of ALS. Thus, the metabolism of sphingolipids is a promising field of study of the processes associated with ALS, both in the context of the search for potential diagnostic markers and effective drugs, and for explaining the pathogenesis of ALS.