BDNF effect on mitochondrial dysfunction induced by 3-nitropropionic acid in striatal astrocytes

FEDERICO LÓPEZ COUSELO; JULIETA SABA; JUAN TURATI; DELIA RAMÍREZ; LILA CARNIGLIA; DANIELA DURAND; MERCEDES LASAGA; CARLA CARUSO

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2018

Sociedad Argentina de Investigación Clínica (SAIC)

Huntington disease (HD) promotes oxidative stress, mitochondrial dysfunction and neurotoxicity that primarily affect the striatum. 3-nitropropionic acid (3-NP), generates mitochondrial dysfunction and oxidative stress as it occurs in HD. High levels of reactive oxygen species (ROS) produced in the mitochondrial matrix generate oxidative stress which is associated with neuronal death. Uncoupling proteins (UCP) are proton transporters of the inner mitochondrial membrane that uncouple the electron transport chain from oxidative phosphorylation. UCP4, which is expressed in astrocytes, seems to be involved in the reduction of mitochondrial ROS levels and UCP4 overexpression protects neurons from mitochondrial dysfunction. We have previously shown that brain-derived neurotrophic factor (BDNF) reduces ROS levels and prevents cell death induced by 3-NP in cortical astrocytes. Now, we studied BDNF effect on striatal astrocyte viability, ROS production and UCP4 expression. We found that BDNF had a significant protective effect on 3-NP-induced death of striatal astrocytes determined by trypan blue exclusion (p<0.01). Also, BDNF reduces the increase in ROS levels induced by 3-NP in striatal astrocytes using a DCFH-DA assay (p<0.001). UCP4 protein levels were determined in cortical and striatal astrocytes by western blot. We show that, in both astrocyte populations, BDNF per se increased UCP4 expression (p<0.05) whilst 3-NP alone reduced it (p<0.05). In the presence of BDNF, 3-NP inhibitory effect on UCP4 expression is not observed. In conclusion, we show that BDNF protects striatal astrocytes from 3-NP toxicity reducing ROS levels and increasing UCP4 expression. These actions could represent new mechanisms of action of BDNF protection.