The role of REST/NRSF, TrkB and BDNF in neurobiological mechanisms of different susceptibility to seizure in a PTZ model of epilepsy.

Global transcriptional disturbances are believed to play a major role in the course of epilepsy. Due to the high complexity, the neurobiological mechanisms underlying different susceptibility to seizure and epilepsy are not well known. A transcription factor called REST/NRSF (repressor element 1-silencing transcription factor/neuron-restrictive silencer factor) is believed to contribute to processes associated with seizure development. Its downstream genes, those encoding BDNF (brain-derived neurotrophic factor) and TrkB (BDNF receptor; tropomyosin receptor kinase B), are also thought to play a role. To verify this hypothesis, we used a PTZ kindling model of epilepsy and divided animals into groups according to their different susceptibility to seizure. The concentrations of REST/NRSF, BDNF, and TrkB protein and mRNA were measured in hippocampal homogenates. The level of REST/NRSF protein measured 24 h after the last PTZ injection was increased in animals resistant to kindling and was unchanged in groups of rats kindled after 5, 10 and 20 in.ections of PTZ. In contrast, TrkB protein concentration was enhanced in all kindled rats and was unchanged in the resistant rats. There were no changes in the protein concentration of BDNF in rats with different susceptibility to kindling; however, data from the combined kindled groups vs. the resistant group revealed an increased level of BDNF in resistant animals. In sum, the increased level of protein REST/NRSF in resistant animals may reflect its neuroprotective role against seizure development. The increased concentration of TrkB protein in kindled animals indicates its pivotal role in the process of epileptogenesis. We propose that in resistant rats, REST/NRSF could contribute to the prevention of TrkB activation related to seizures.