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

MONTROULL, LAURA ESTER; MASCÓ, DANIEL HUGO

New Orleans

Congreso; 42nd Annual Meeting of the Society for Neuroscience; 2012

Society for Neuroscience

Brain-Derived Neurotrophic Factor (BDNF) has been implicated in several aspects of adult hippocampus physiology. BDNF is initially synthesized as a precursor proBDNF that may be cleaved intra or extracellularly. BDNF promotes survival of TrkB receptor tyrosine kinase expressing neurons, while proBDNF can bind to a complex of p75ntr and sortilin receptors to induce apoptosis. We have previously shown that status epilepticus (SE) induces neuronal death, a decrease in TrkB expression, and a signaling switch from BDNF-TrkB to BDNF-p75ntr and proBDNF-p75ntr in the CA1 region of the hippocampus. We hypothesize that this receptors switch has a key role in the development of the seizure-induced neuronal death in the hippocampus. To test this, we infused unilaterally TrkB-Fc (a BDNF scavenger) in the CA1 region of the hippocampus immediately after the SE. Animals were sacrificed 24h later and TrkB and phospho-TrkB levels were analyzed by western blot and neuronal damage was assessed by Fluoro-Jade B. We found that TrkB-Fc prevents the decrease in TrkB levels. Moreover, we found a decrease in phospho-TrkB in both hippocampi (ipsi and contralateral to the TrkB-Fc administration) and an increase in neuronal death in the ipsilateral CA1 region. These results indicate that released BDNF is able to decrease the levels of TrkB, and this scenario could facilitate BDNF and proBDNF binding to p75ntr leading to neuronal death.