Genistein Inhibits Aβ-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 β-Amyloid peptide fragment 25-35, Aβ. We then observed the effects of genistein, a type of soybean isoflavone, on Aβ-incubated hippocampal neuron viability, and the electrophysiological properties of voltage-gated sodium channels (Na) and potassium channels (K) in the hippocampal neurons. Aβ exposure reduced the viability of hippocampal neurons, decreased the peak amplitude of voltage-activated sodium channel currents (I), and significantly reduced I at different membrane potentials. Moreover, Aβ shifted the activation curve toward depolarization, shifted the inactivation curve toward hyperpolarization, and increased the time constant of recovery from inactivation. Aβ exposure significantly shifted the inactivation curve of transient outward K currents (I) toward hyperpolarization and increased its time constant of recovery from inactivation. In addition, Aβ significantly decreased the peak density of outward-delayed rectifier potassium channel currents (I) and significantly reduced I 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 and K induced by Aβ. Our results suggest that genistein could inhibit Aβ-induced neuronal damage with changes in the electrophysiological properties of Na and K.