Investigation of the effects of neurotrophin receptors TrkB and p75 on epilepsy-like events induced in brain slices

Neurotrophic factors are messenger/modulator proteins that play a role in processes such as brain development, regulation of functions, control of nerve cell branching and brain-derived neurotrophic factor (BDNF) is one of these neurotrophic factors. In the central nervous system (CNS), tropomyosin receptor kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) are receptors of BDNF. While the TrkB receptor shows affinity for the mature form of BDNF, p75NTR shows affinity for both the mature and pro forms of BDNF. These receptors generally play a role in events such as nerve cell development, survival, differentiation and plasticity of nerve cells. However, the fact that p75NTR has different ligands has made it also responsible for cell death. Neuronal excitability refers to the tendency of a neuron to reach its firing threshold. Excitability increases in epilepsy, causing neurons to produce electrical activity more easily and uncontollably than normal. The aim of this study was to investigate the acute effects of ANA-12, which antagonizes the TrkB pathway, and LM11A-31, which stops the p75 pathway, on neural activities associated with epilepsy. In the in vitro epilepsy model, horizontal fresh brain slices containing the hippocampus and entorhinal cortex regions were obtained using C57BL/6 wild type mice. Simultaneous recordings were made from the hippocampus (CA1) and entorhinal cortex regions. Epilepsy-like events were induced in the slices with application of 4-AP (100 μM). How ANA-12 (10 μM) and LM11A-31 (100 nM) molecules affected normal neural activity and epilepsy-like events was evaluated separetely with the help of electrophysiological data. Power spectrum analyses, frequencies, durations and amplitudes of epileptic activities were calculated from the obtained data. The values of the substances before and after application to the sections were compared. In the 0.1-50 Hz bandwidth, the molecules didn't change strengths (mV2/Hz) of epileptic-like events in the hippocampus and entorhinal cortex. The frequencies and durations of epileptic-like events decreased in both brain regions after ANA-12 application. LM11A-31 application didn't affect frequencies, durations and amplitudes of epileptic-like events.