Genistein Inhibits Aβ25–35-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 β-Amyloid peptide fragment 25–35, Aβ25–35. We then observed the effects of genistein, a type of soybean isoflavone, on Aβ25–35-incubated hippocampal neuron viability, and the electrophysiological properties of voltage-gated sodium channels (NaV) and potassium channels (KV) in the hippocampal neurons. Aβ25–35 exposure reduced the viability of hippocampal neurons, decreased the peak amplitude of voltage-activated sodium channel currents (INa), and significantly reduced INa at different membrane potentials. Moreover, Aβ25–35 shifted the activation curve toward depolarization, shifted the inactivation curve toward hyperpolarization, and increased the time constant of recovery from inactivation. Aβ25–35 exposure significantly shifted the inactivation curve of transient outward K+ currents (IA) toward hyperpolarization and increased its time constant of recovery from inactivation. In addition, Aβ25–35 significantly decreased the peak density of outward-delayed rectifier potassium channel currents (IDR) and significantly reduced IDR value at different membrane potentials. We found that genistein partially reversed the decrease in hippocampal neuron viability, and the alterations in electrophysiological properties of NaV and KV induced by Aβ25–35. Our results suggest that genistein could inhibit Aβ25–35-induced neuronal damage with changes in the electrophysiological properties of NaV and KV.