Disorder of myelinization in the spinal cord of transgenic mSOD1 mice as one of the mechanisms pathogenesis of amyotrophic lateral sclerosis

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Abstract

Amyotrophic lateral sclerosis (ALS) is a disease characterized by progressive muscle weakness, atrophy, spasticity, paralysis caused by degeneration and death of motor neurons in the brain and spinal cord, leading to death. Model animals such as SOD1-G93A mice expressing a human mutation of the gene encoding the antioxidant enzyme superoxide dismutase 1 are widely used to study the pathogenesis of ALS and its treatment. Transgenic mice exhibit disease phenotypes similar to ALS patients, expressed in motor function impairment, motor neuron degeneration in the spinal cord, brainstem, and cortex, leading to paralysis of the hind limbs and death. In the present work, the areas of transverse serial sections of the lumbar enlargement of the spinal cord, as well as the areas occupied by white and gray matter in these sections were estimated using light microscopy in wild-type WT mice and transgenic mSOD1 mice at different stages of ALS development. The revealed reduction in the volume of the lumbar enlargement of the spinal cord in transgenic mice is detected already at the early presymptomatic stage of the disease and 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 spinal cord, a characteristic sign of ALS caused by the death of these cells, was detected in transgenic mice only at the symptomatic stage of the disease. Using fluorescence microscopy, a decrease in the fluorescence intensity of fluoromyelin, a specific myelin dye, in the white matter of the lumbar enlargement of the spinal cord in transgenic mice was established starting from the early presymptomatic stage. The revealed morphological changes in the lumbar spinal cord of transgenic mSOD1 mice allow us to conclude that already at the early pre-symptomatic stage of ALS, demyelination processes develop, most likely arising as a result of disruption of the functioning of myelin-forming cells.

About the authors

O. V. Tyapkina

Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS; Kazan State Medical University

Email: anti-toxin@mail.ru
Kazan, Russia; Kazan, Russia

M. A. Mukhamedyarov

Kazan State Medical University

Kazan, Russia

L. F. Nurullin

Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS; Kazan State Medical University

Kazan, Russia; Kazan, Russia

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