INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TrkB receptor mediates BDNF protection of astrocytes
Autor/es:
JUAN TURATI; MERCEDES LASAGA; DELIA RAMÍREZ; DANIELA DURAND; JULIETA SABA; CARNIGLIA, LILA; CARLA CARUSO
Lugar:
Paris
Reunión:
Congreso; 26th ISN ESN biennal meeting; 2017
Institución organizadora:
ISN ESN
Resumen:
Brain-derived neurotrophic factor (BDNF) is a neurotrophin that promotes neuronal survival and inhibits apoptosis. Since little is known about BDNF action in astrocytes, we examined the effect of BDNF on astrocyte viability and the involvement of TrkB in this action. BDNF treatment for 24 h increased astrocyte viability by reducing apoptosis induced by serum deprivation (SD). BDNF also reduced p53 and active caspase-3 expression induced by SD. Next, we determined TrkB participation by using the selective and potent TrkB antagonist ANA-12 (which inhibits TrkB- full length (TrkB-FL) and TrkB-Truncated1 (TrkB-T1) isoforms) or K252a which is a tyrosine kinase inhibitor of TrkB-FL receptors. The presence of each inhibitor blocked the decrease in cell death induced by BDNF. In order to identify which TrkB isoform is involved in BDNF protective effect we analyzed mRNA expression levels of TrkB-FL and TrkBT1 by RT-qPCR, both isoforms TrkB-FL and TrkB-T1 are expressed in cultured astrocytes although TrkB-FL is expressed at lower levels than TrkB-T1. Western Blot of TrkB showed that only TrkB-T1 protein is present in cultured astrocytes. Thus, although astrocytes express mRNA for TrkB-FL, this is not translated into detectable protein levels in these cells. However, BDNF induced ERK activation in astrocytes and blocking this pathway abolished BDNF protection from SD-induced apoptosis. Finally, we evaluated if BDNF could protect astrocytes from 3-nitropropionic acid (3NP)-induced cell death, being 3NP a toxin widely used as an in vitro model of Huntington?s disease. We found that BDNF prevented astrocyte death induced by 3NP and this effect was blocked by both TrkB and ERK inhibitors. In conclusion, our results indicate that TrkB mediates BDNF antiapoptotic effect on astrocytes through ERK activation. Since astrocytes are key players in neuroprotection, understanding BDNF protective mechanisms in these cells may help develop new strategies for treating neurodegeneration.