IIBYT   23944
INSTITUTO DE INVESTIGACIONES BIOLOGICAS Y TECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
TrkB signaling has a key role in survival in a model of Status Epilepticus
Autor/es:
MASCÓ, DANIEL H; LAURA MONTROULL,; DANELON, VÍCTOR
Reunión:
Congreso; IBRO Congress 2015; 2015
Resumen:
Neurotrophins are secretory proteins that bind to target receptorsinfluencing survival activity. Brain-Derived Neurotrophic Factor(BDNF) is initially synthesized as proBDNF that is cleaved to releasethe mature form. BDNF binds to TrkB leading to neuron survival andproBDNF interact with p75ntr leading to apoptosis (Teng et al, 2010).Many studies have demonstrated that seizures induce changes inthe expression of NT, pro-NT and their receptors (Friedman 2010).The administration of pilocarpine to rats pre-treated with lithiumleads to a prolonged-seizures condition called Status Epilepticus(SE), and results in both necrotic and apoptotic cell death in variousbrain areas. SE also serves as a model of Temporal Lobe Epilepsywith hippocampal sclerosis, the most frequent epilepsy in humans(Curia et al, 2008). The in vitro model of SE is based on the physiologyof the NMDA receptor (Sombati and DeLorenzo, 1995). This receptoris permeable to sodium and potassium ions, but also it is for calciumions. Therefore a feature of SE is the increase in intracellular calciumconcentration in hippocampal neurons due to massivehyperactivation of this receptor and the consequent neuronaldeath.We have previously shown that 3h of neuronal hyperactivation in aco-culture of hippocampal neurons and astrocytes inducesneuronal death and SE in vivo induced a rapid down-regulation ofTrkB that precedes neuronal death in the CA1 and a switch amongBDNF/TrkB to BDNF/p75ntr and proBDNF/p75ntr binding (Unsain et al,2008). We hypothesize that the decrease in TrkB signaling has a keyrole in the development of neuronal death.