Although neurotrophic pathways and epigenetic processes are believed to be significant contributors to epileptogenesis and
epilepsy,
therapies using modulators of these targets are still lacking.
BDNF-TrkB-mTOR signalling and the REST/NRSF-coREST-HDAC2 system are critical pathways responsible for neurotrophic and epigenetic processes, respectively. In our study, we assessed whether these two pathways are activated in a kindling model of
seizures. We assessed the
protein and
mRNA levels of
BDNF, TrkB, mTOR, REST/NRSF, coREST and HDAC2 in the brain. The study results showed increased expression of
BDNF and decreased coREST in rats subjected to electrical kindling compared to control animals. We also revealed increased expression of both mTOR and HDAC2 in the brain tissue of electrically stimulated animals.
mRNA production did not follow the intensified mTOR and HDAC2
protein synthesis. Furthermore, increased expression of
BDNF, mTOR and HDAC2 was observed in animals that did not fulfil the kindling criteria in comparison to fully kindled rats. In conclusion, our results suggest that during epileptogenesis, the
BDNF/mTOR neurotrophic pathway is mainly activated, with TrkB playing a less important role. Furthermore, the epigenetic
transcription factor REST/NRSF was not found to be critical for HDAC2 activation. The simultaneous activation of both mTOR and HDAC2 systems during epileptogenesis confirms multifactorial neuronal adaptation, including neurotrophic and epigenetic processes. Our results may indicate that similar to
cancer studies, the coadministration of regulators of both system should be considered a new potential strategy for preventing epileptogenesis.