Maltodextrin administration ameliorates brain pathology in a mouse model of mitochondrial disease

Abstract

AbstractMitochondrial dysfunction lead to a wide group of progressive and fatal pathologies known as mitochondrial diseases (MD). One of the most common pediatric representation of MD is Leigh Syndrome, affecting 1/40.000 births. LS is characterized by neurodegeneration in specific brain areas, such as brainstem and basal ganglia, and by respiratory and motor alterations. However, the results obtained from clinical trials based on antioxidant therapies are controversial. Thus, the development novel antioxidant strategy is required to improve the efficacy of current palliative treatments. In this regard, Ndufs4KO mouse model is a suitable model to test new drugs in the field of MD and LS. Therefore, we set to assess the therapeutic potential of oral administration ofMicrococcus luteus, a high-antioxidant content microorganism. Incidentally, we identified that whileM. luteusadministration did not possess any beneficial actions, the cryopreservant maltodextrin (MDX), included in the preparation, ameliorated the phenotype of Ndufs4KO mice. Our results show that MDX treatment at a concentration of 30 g/L increased lifespan and reduced microglial reaction compared to vehicle-treated Ndufs4KO mice. However, no improvement in locomotion nor respiratory function was observed in MDX-treated mice compared to vehicle-treated Ndufs4KO mice. Metataxonomic characterization of intestinal microbiome identified differential profiles in Ndufs4KO mice at the genus level. Furthermore, MDX treatment increased the variability of the abundance ofAkkermansia sp. Thus, this work paves the way for further studies to confirm the therapeutic potential of MDX in mitochondrial disease.