Blocking BDNF inhibits TrkB receptor phosphorylation and induces an increase in neuronal death after Status Epilepticus

MONTROULL, LAURA ESTER; MASCÓ, DANIEL HUGO

Huerta Grande - Córdoba

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia; 2011

Sociedad Argentina de Investigación en Neurociencia

Brain-Derived Neurotrophic Factor (BDNF) has been implicated in several aspects of adult hippocampus physiology. BDNF is initially synthesized as proBDNF and its interaction with his receptor TrkB has been implicated in neuronal survival, while proBDNF with p75ntr/sortilin in apoptosis. We previously showed that cell death induced by Status Epilepticus (SE) produce a decrease in TrkB membrane expression and a switch BDNF/TrkB to BDNF/p75ntr binding. We hypothesize that this phenomenon has a key role in the development of neuronal death.To test this we administrated unilaterally TrkB-Fc (a BDNF scavenger) in the CA1 region of hippocampus immediately after SE. Animals were sacrificed 24h later and TrkB and pTrkB levels were analyzed by Western Blot. Neuronal damage was assessed by FJB. We found that TrkB-Fc only blocks BDNF and not proBDNF, and therefore could prevent the decrease in the levels of TrkB while not in pTrkB levels. These results indicate that BDNF release is able to produce the decrease of its own TrkB receptor and in this scenario facilitate its binding with p75ntr/sortilina. These results strongly suggest that BDNF induce cell death only in the absent of TrkB signaling.