Synaptic Vesicle Exocytosis and Endocytosis in Motor Nerve Endings of Transgenic Mice Modeling Amyotrophic Lateral Sclerosis upon Antioxidant Treatment and Gene-Cell Therapy

P. N. Grigoryeva, Academician of the RAS A. L. Zefirova, R. D. Mukhamedzyanova, I. I. Salafutdinovb, R. R. Islamova, and M. A. Mukhamedyarova*

aKazan State Medical University, Ministry of Health of the Russian Federation, Kazan, Russia

bKazan (Volga) Federal University, Kazan, Russia

*email: marat.muhamedyarov@kazangmu.ru

Received August 15, 2025

Abstract— Exocytosis and endocytosis of synaptic vesicles were studied in experiments with motor nerve endings of diaphragm neuromuscular preparations isolated from transgenic mice with a model of amyotrophic lateral sclerosis (ALS); treatment simulated antioxidant (edaravone) and gene-cell (umbilical cord blood mononuclear cells (UCB-MNCs) producing VEGF, GDNF, and NCAM) therapies. None of the treatments was found to significantly change the FM 1-43 fluorescent dye loading due to synaptic vesicle endocytosis. Gene-cell therapy increased the rate of dye unloading due to synaptic vesicle exocytosis, while antioxidant therapy did not change the FM 1-43 unloading rate. Based on the findings, gene-cell therapy was assumed to facilitate synaptic vesicle transport to release sites upon high-frequency stimulation in motor nerve endings of transgenic mice.

Keywords: amyotrophic lateral sclerosis, transgenic mice, antioxidant therapy, gene-cell therapy, neuromuscular junction, exocytosis and endocytosis of synaptic vesicles

DOI: 10.1134/S0012496625600356