Genistein Inhibits A Beta(25-35)-Induced Neuronal Death With Changes In The Electrophysiological Properties Of Voltage-Gated Sodium And Potassium Channels

We established a model of Alzheimer's disease in vitro by exposing primary hippocampal neurons of neonatal Wistar rats to the -Amyloid peptide fragment 25-35, A(25-35). We then observed the effects of genistein, a type of soybean isoflavone, on A(25-35)-incubated hippocampal neuron viability, and the electrophysiological properties of voltage-gated sodium channels (Na-V) and potassium channels (K-V) in the hippocampal neurons. A(25-35) exposure reduced the viability of hippocampal neurons, decreased the peak amplitude of voltage-activated sodium channel currents (I-Na), and significantly reduced I-Na at different membrane potentials. Moreover, A(25-35) shifted the activation curve toward depolarization, shifted the inactivation curve toward hyperpolarization, and increased the time constant of recovery from inactivation. A(25-35) exposure significantly shifted the inactivation curve of transient outward K+ currents (I-A) toward hyperpolarization and increased its time constant of recovery from inactivation. In addition, A(25-35) significantly decreased the peak density of outward-delayed rectifier potassium channel currents (I-DR) and significantly reduced I-DR value at different membrane potentials. We found that genistein partially reversed the decrease in hippocampal neuron viability, and the alterations in electrophysiological properties of Na-V and K-V induced by A(25-35). Our results suggest that genistein could inhibit A(25-35)-induced neuronal damage with changes in the electrophysiological properties of Na-V and K-V.