Effects of blocking ryanodine receptors on epileptiform activity in vivo

Abstract

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that directly interferes with a patient's quality of life. The occurrence of an epileptic status (ES), a clinical condition in which repeated or prolonged crises are present, is one of the causes that can lead to the development of TLE. The development and maintenance of TLE involve processes dependent on the concentration of intracellular calcium levels, which can be released from intracellular stores such as the endoplasmic reticulum (ER). There is evidence that ES leads to an increase in Ca2 + in hippocampal neurons, and ryanodine receptors (RyRs), channels present in the ER that control the release of calcium into the cytoplasm, are involved in this increase. In addition to the participation of calcium in the processes involved with epileptogeneses, such as neuronal death, aberrant synaptic plasticity, and neurogenesis, changes in intracellular Ca2 + homeostasis play a fundamental role in the generation and spread of epileptiform events. Therefore, strategies that promote the reduction of epileptic seizures, in conjunction with the action on cellular and molecular targets involved with epileptogenesis are of great clinical interest. Thus, this project aims to assess the contribution of RyRs to ictal activity during SE induced by pilocarpine in rats, combining electrophysiological records in vivo and pharmacological manipulation of RyRs. With this project, it is hoped to elucidate the participation of RyRs in epileptiform activity in the hippocampus of rats, as a subsidy for future therapeutic interventions.