Comparative Study of Structural and Functional Rearrangements in Skeletal Muscle Mitochondria of SOD1-G93A Transgenic Mice at Pre-, Early-, and Late-Symptomatic Stages of ALS Progression

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(3)

Published: March 18, 2025

Background: Amyotrophic lateral sclerosis (ALS) is a progressive multisystem disease characterized by limb and trunk muscle weakness that attributed, in part, to abnormalities mitochondrial ultrastructure impaired functions. This study investigated the time course of structural functional rearrangements skeletal mitochondria combination with motor impairments Tg (copper-zinc superoxide dismutase enzyme (SOD1) G93A) dl1/GurJ (referred as SOD1-G93A/low) male mice, familial ALS model, compared non-transgenic littermates. Methods: The neurological status functions were assessed weekly using paw grip endurance method grid suspension test two-limb four-limb tasks. Transmission electron microscopy followed quantitative analysis was performed ultrastructural alterations quadriceps femoris. Functional high-resolution Oxygraph-2k (O2K) respirometry methods for assessing calcium retention capacity index content lipid peroxidation products freshly isolated preparations. Results: Based on behavioral phenotyping data, specific age groups identified: postnatal day 56 (P56) (n = 10–11), 84 (P84) 156 (P154) 10–12), representing pre-symptomatic, early-symptomatic late-symptomatic stages progression SOD1-G93A/low respectively. Electron showed mosaic destructive changes subsarcolemmal fibers femoris from 84-day-old mice. Morphometric revealed an elevation mean size SOD1-G93A mice at P84 P154. In addition, P154 transgenic group demonstrated decrease sarcomere width number per unit area. At symptomatic stage, exhibited decreased respiratory control ratio, ADP-stimulated, uncoupled respiration rates muscle, measured respirometry. parallel, lower increased levels control. Conclusions: Taken together, these results indicate stage-dependent associated defective oxidative phosphorylation, homeostasis, damage mouse which appears be promising direction development therapies ALS.

Language: Английский

Critical issues in the use of edaravone for the treatment of amyotrophic lateral sclerosis

Neurological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: April 8, 2025

Language: Английский

Unlocking the future: Precision oligonucleotide therapy for targeted treatment of neurodegenerative disorders

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 143515 - 143515

Published: April 1, 2025

Language: Английский