Abstract: Epilepsy is a seizure disorder characterized by spontaneous recurrent seizures (SRS). The complexity of epilepsy is broadened by a brain injury associated with episodes of prolonged continuous seizures (status epilepticus) (SE) that per se can increase the risk for the development of SRS, temporal lobe epilepsy, and cognitive deficits. Studies in well-established rodent models of epilepsy support that SE provokes changes in the vulnerable hippocampal circuitry that include acute and progressive neuronal decline with disruptions in dendritic arborizations with spine/synapse loss, and microgliosis. These in turn may promote neuronal hyperexcitability and abnormal hippocampal-dependent learning and memory. Candidate mechanisms underlying the neuropathology of epilepsy include the mechanistic target of rapamycin (mTOR) signaling cascade. Under physiological conditions neuronal mTOR signaling regulates protein synthesis, dendritic and axonal growth, synaptic plasticity, and memory. Also, extensive evidence implicates aberrant hyperactivated mTOR signaling in the neuropathology of many neurological disorders including epilepsy. Thus, using experimental models of genetic and acquired epilepsy we examined the role of mTOR signaling in SRS, epileptiform activity, excessive axonal and cellular growth, dendritic alterations, and memory deficits. We found that pharmacological suppression of mTOR signaling attenuated some of these pathologies and also remarkably reduced inflammatory activation of microglial cells. Taken together our findings suggest that mTOR-dependent microglial properties may play critical roles in the pathophysiology of epilepsy.

~BME Faculty Host: Pedro Irazoqui~

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