BDNF effect on oxidative stress in cortical and striatal astrocytes and in striatal neurons expressing mutant huntingtin

FEDERICO LÓPEZ COUSELO; JULIETA SABA; JULIETA BRUNO; LILA CARNIGLIA; DANIELA DURAND; MERCEDES LASAGA; CARLA CARUSO

Schmerlenbach

Workshop; ISN-JNC Flagship School 2022; 2022

Internation Society for Neurochemistry

Huntington’s disease (HD) involves mitochondrial dysfunction which can be mimicked by 3-nitropropionic acid (3NP). Reactive oxygen species (ROS) generate oxidative stress which is associated with neuronal death. Glutathione (GSH) is an antioxidant molecule secreted mostly by astrocytes that can protect neurons by reducing ROS levels. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme and the uncoupling protein 4 (UCP4) is a proton transporter of the inner mitochondrial membrane. Both are involved in the reduction of ROS levels and their overexpression provides neuroprotection. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that exerts protective effects in HD models. We have already shown that BDNF reduces ROS levels induced by 3NP and increases intracellular GSH while 3NP reduces extracellular GSH levels in total cultured rat astrocytes. We now examined BDNF effect on oxidative stress induced by 3NP in cortical and striatal astrocytes. In both astrocyte populations we found that, BDNF reduced ROS levels increased by 3NP (p