Brain-derived neurotrophic factor protects astrocytes from cell death

JULIETA SABA; DELIA RAMIREZ; LILA CARNIGLIA; DANIELA DURAND; MERCEDES LASAGA; CARLA CARUSO

Mar del Plata

Congreso; XXX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal survival and inhibits apoptosis of neurons and oligodendrocytes. Nevertheless, little is known about BDNF effects on astrocytes. We have previously shown that BDNF increases astrocyte viability through ERK and Akt pathways. Now, we studied the effects of BDNF on astrocyte death. Primary cultures of rat astrocytes were incubated for 24 h with or without BDNF 50 ng/ml and apoptosis was induced by serum deprivation. We found that BDNF blocked the decrease in cell viability induced by serum deprivation. BDNF decreases the percentage of hypodiploid (Sub G1) astrocytes and the percentage of TUNEL-positive astrocytes induced by serum deprivation. The BDNF receptor (TrkB) antagonist, ANA12,blocked the protective effects of BDNF. We also treated astrocytes with 3-nitropropionic acid (3NP), a toxin widely used as an in vitro model of Huntington?s disease. 3NP decreased astrocyte viability in a dose-dependent manner. BDNF abolished the inhibitory effect of 3NP on astrocyte viability. Next, we treated PC12 neurons with 3NP to induce neuronal death. Conditioned medium from BDNF-treated astrocytes blocked the decrease in PC12 neuron viability induced by 3NP. These results indicate that BDNF protects astrocytes from different insults by engaging TrkB, and that BDNF-treated astrocytes have neuroprotective actions in a model of Huntington disease.