Protective effects of diarylpropionitrile against hydrogen peroxide-induced damage in human neuroblastoma SH-SY5Y cells

S495poorly understood.We have used human cortical neurons derived from induced pluripotent stem cells (iPSC) from FTDP-17 patients and carried out an electrophysiological study to compare neuronal properties and intrinsic excitability between FTDP-17 and control (healthy volunteers).We document the phenotypic patterns of neuronal activity in FTDP-17 (recorded in either cell-attached or whole-cell mode) which represent characteristic bursts of spontaneous firing activity followed by periods of action potential (AP) silence.For the membrane properties, the resting membrane potential was, on average, depolarized in cortical neurons in FTDP-17 compared to control (at ∼150 DIV).This caused sustained depolarization after spontaneous AP firing and impaired shaping individual APs.Overall changes could be associated with the increased functional expression of ionotropic glutamate receptors of AMPA and NMDA types, seen as the augmented glutamate-induced currents in FTDP-17.The observed changes were accompanied by the synaptic (network) hyperexcitability mediated by AMPAR activation.Taken together, our results demonstrate the impairment of glutamatergic signaling mediating functional deficits in cortical neurons that may play a critical role in the pathophysiology of FTDP-17.