BDNF’S ANTIOXIDANT EFFECT ON OXIDATIVE STRESS IN THE ZQ175 MOUSE MODEL OF HUNTINGTON'S DISEASE

FEDERICO LÓPEZ COUSELO; JULIETA SABA; MATEO PALMIERI; JULIETA BRUNO; DIEGO RIVAS; MARÍA FRISER; LILA CARNIGLIA; DANIELA DURAND; MERCEDES LASAGA; CARLA CARUSO

Toronton

Workshop; MDS-PAS Translating Science into Solutions for Movement Disorders; 2024

International Parkinson and Movement Disorder Society

Huntington's disease (HD) is a progressive neurodegenerative genetic disorder caused by a CAG repeat expansion inthe huntingtin gene that primarily affects the striatum and later the cortex, resulting in cognitive impairment and motordysfunction. Oxidative stress, mitochondrial dysfunction, and neurotoxicity are proposed as pathogenic mechanisms.Oxidative stress is generated by high levels of reactive oxygen species (ROS), which can be reduced by antioxidantmolecules such as glutathione (GSH) and the activity of the mitochondrial enzyme superoxide dismutase 2 (SOD2).Uncoupling proteins 2 and 4 (UCP2-4) are proposed to minimize mitochondrial ROS via proton gradient dissipation.Brain-derived neurotrophic factor (BDNF) is a neurotrophin that exerts protective effects in HD models. Our goal was todetermine the effect of BDNF on the oxidative stress of zQ175 (HD mice), a knock-in mouse model of HD that has notbeen tested for oxidative stress. Initially, we evaluated weight gain, motor performance and behavior (open field andnovel object recognition tests), ROS and GSH levels (DCFH-DA and NDA assays, respectively), as well as UCP2, UCP4and SOD2 expression (Western blot) in the striatum and cortex of WT and HD mice at the ages of 4 months (4m) and 8months (8m). HD mice showed reduced motor performance and memory deficits starting at 4m (p