Abstract <p>Amyotrophic lateral sclerosis (ALS) is a disease characterizedby progressive muscle weakness, atrophy, spasticity, and paralysis,caused by the degeneration and death of motor neurons in the brain andspinal cord, and leading to a fatal outcome. Model animals, suchas SOD1-G93A mice expressing a mutation in the gene encoding theantioxidant enzyme superoxide dismutase 1, are widely used to study ALSpathogenesis and potential treatments. Transgenic mice exhibit diseasephenotypes similar to ALS patients, manifested by motor dysfunction,degeneration of motor neurons in the spinal cord, brainstem, andcortex, leading to hindlimb paralysis and death. In the presentstudy, the areas of serial transverse sections of the lumbar enlargementof the spinal cord, as well as the areas occupied by white and gray matterin these sections, were assessed in wild-type (WT) mice and transgenicmSOD1 mice at different stages of ALS development using light microscopy.The revealed reduction in the lumbar enlargement volume in transgenicmice occurs already at the early presymptomatic stage of the diseaseand is due to a decrease in the volumes of both gray and white matter.A decrease in the number of neurons in the gray matter of the spinalcord, an ALS hallmark caused by the death of these cells, was detectedin transgenic mice only at the symptomatic stage of the disease.Using fluorescence microscopy, a decrease in the fluorescence intensityof the myelin-specific dye Fluoromyelin in the white matter of thelumbar enlargement was detected in transgenic mice, starting fromthe early presymptomatic stage. The identified morphological alterationsin the lumbar spinal cord of transgenic mSOD1 mice suggest that demyelinationprocesses develop already at the early presymptomatic stage of ALS,most likely resulting from the dysfunction of myelin-producing cells.</p>