Intensity-dependent gamma electrical stimulation regulates microglial activation, reduces beta-amyloid load, and facilitates memory in a mouse model of Alzheimer’s disease

Abstract

Abstract Background: Gamma electrical stimulation (GES) may reduce AD-specific pathology. Yet, the efficacy of electrical stimulation in animal models of AD is unknown, and prior research has not addressed intensity-dependent effects. Objective: The effect of GES on Aβ clearance and microglia modulation were assessed in 5xFAD mouse brain, as well as the behavioral performance of the animals in the Morris Water Maze. Methods and Results: One hour of epidural GES at 40Hz delivered over a month significantly 1) reduced Aβ42 load in the AD brain, 2) increased microglia cell counts, decreased cell body size, increased length of cellular processes of the Iba1+ cells, and 3) improved behavioral performance (learning & memory). All these effects were most pronounced when a higher stimulation current was applied. Conclusion: The efficacy of GES on the reduction of AD pathology and the intensity-dependent feature provides guidance for the development of this promising therapeutic approach.