A FATAL AFFAIR: BDNF LEAVES TRKB FOR P75NTR AFTER SEIZURES

UNSAIN NICOLÁS; MASCÓ DANIEL HUGO

Pinamar, Buenos Aires, Argentina

Congreso; Reunión Anual Sociedad Argentina de Investigación en Neurociencias; 2005

SAN - Sociedad Argentina de Investigación en Neurociencias

Brain-derived neurotrophic factor (BDNF) actions through the common neurotrophin receptor p75 (p75ntr) has been associated with neuronal death, while its binding to the TrkB receptor to neuronal survival. Status Epilepticus (SE) is a condition in which prolonged seizures causes neuronal apoptosis in the hippocampus. It has been suggested that p75ntr is involved in this neuronal death, however, 1) there are no studies showing increased binding of BDNF to p75ntr after seizures and 2) BDNF binding to TrkB should decrease given that its signalling overrides p75ntr activity and that we found a decrease in TrkB protein after seizures. Thus, in the present study we performed co-immunoprecipitation assays in hippocampal samples after SE to detect ligand-receptor complexes. Both pro- and mature forms of BDNF were immunoprecipitated (IP) and samples were analyzed by Western blot for the presence of p75ntr and TrkB. We found an increase in co-IP p75ntr at 12 and 72 h after SE. Interestingly, two reactive bands (probably differing in posttranslational modifications) had different peaks of binding to BDNF: the 60kDa band peaked at 12 h, while the 66kDa band peaked at 72 h. On the other hand, TrkB in co-IP samples decreased after SE, and we did not detect truncated TrkB species. The SE-induced up-regulation in the binding of BDNF to p75ntr, with the accompanying down-regulation of its binding to TrkB, suggets a pro-apoptotic role for this neurotrophin after seizures.