Amyloid- Oligomer-Induced Electrophysiological Mechanisms and Electrical Impedance Changes in Neurons

Amyloid plays a critical role in the pathogenesis of Alzheimer's disease (AD) and can aggregate to form oligomers and fibrils in the brain. There is increasing evidence that highly toxic amyloid-beta oligomers (A beta Os) lead to tau protein aggregation, hyperphosphorylation, neuroinflammation, neuronal loss, synaptic loss, and dysfunction. Although the effects of A beta Os on neurons have been investigated using conventional biochemical experiments, there are no established criteria for electrical evaluation. To this end, we explored electrophysiological changes in mouse hippocampal neurons (HT22) following exposure to A beta Os and/or naringenin (Nar, a flavonoid compound) using electrical impedance spectroscopy (EIS). A beta O-induced HT22 showed a decreased impedance amplitude and increased phase angle, and the addition of Nar reversed these changes. The characteristic frequency was markedly increased with A beta O exposure, which was also reversed by Nar. The A beta Os decreased intranuclear and cytoplasmic resistance and increased nucleus resistance and extracellular capacitance. Overall, the innovative construction of the eight-element CPE-equivalent circuit model further reflects that the pseudo-capacitance of the cell membrane and cell nucleus was increased in the A beta O-induced group. This study conclusively revealed that A beta Os induce cytotoxic effects by disrupting the resistance characteristics of unit membranes. The results further support that EIS is an effective technique for evaluating A beta O-induced neuronal damage and microscopic electrical distinctions in the sub-microscopic structure of reactive cells.