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Repeated Exposure to Ozone Produces Changes in Metabolic Disturbances Present in the TDP-43A315T Transgenic Model of Amyotrophic Lateral Sclerosis

Ana Rodriguez, Agueda Ferrer-Donato, Susana Sesena, Paloma Fernández, Alfonso Aranda, Carmen M. Fernandez-Martos

Metabolic abnormalities play a key role in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS). Different drugs have been used in the clinical practice; however, no current therapeutic disease-modifying intervention exists. The biological effect of ozone (O₃) has gained much attention in neurodegenerative disorders, due to its strong capacity to induce controlled oxidative stress and inflammation. However, its effect on metabolism are very less studied, even though O₃ is known for cause endocrine and metabolic changes, increasing food intake and body fat mass. Considering that body weight gain and mild obesity appears to improve survival in ALS patients, the aim of this study was to address the role of O₃ on the metabolic disturbances present in ALS. To test this hypothesis,(4 hours/day). The effect of O₃ exposure on ALS disease progression was addressed by monitoring body weight loss and motor performance until the disease end-stage in ALS mice. Furthermore, we investigated the action of O₃ on plasma glucose content and biomarkers of metabolism by immunoassay. O₃ exposure significantly improves motor performance and mitigates disease-associated weight loss in TDP-43^A315T mice. As well, circulating levels of TDP-43^TDP-43A315T mice and age-matched WT ittermates, were exposed to O₃ (0.25 ppm) or filtered air (FA) for 15 days metabolic proteins and glucose in plasma were highest at disease end-stage after O exposure in TDP-43^A315T mice. These findings provide the first insights into the mechanistic link between O₃ exposure and the improvement of the metabolic disturbances present in ALS, based on experimental data.