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

Abstract

Background Gamma sensory stimulation may reduce AD-specific pathology. Yet, the efficacy of alternating electrical current stimulation in animal models of AD is unknown, and prior research has not addressed intensity-dependent effects. Methods The intensity-dependent effect of gamma electrical stimulation (GES) with a sinusoidal alternating current at 40 Hz on Aβ clearance and microglia modulation were assessed in 5xFAD mouse hippocampus and cortex, as well as the behavioral performance of the animals with the Morris Water Maze. Results One hour of epidural GES delivered over a month significantly (1) reduced Aβ 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 provide guidance for the development of this promising therapeutic approach.

Transcriptomic analysis of rat brain response to alternating current electrical stimulation: unveiling insights via single‐nucleus RNA sequencing

“…Our work contributed to this discussion, showing that electric stimulation can promote neuronal differentiation from neural stem cells, and enhance endogenous neurogenesis in healthy and AD rat brain. 21 , 22 , 28 For the underlying molecular mechanism, we have observed the phosphoinositide‐3‐kinase (PI3K)/Akt (also called protein kinase B or PKB)/Glycogen xynthase kinase‐3 beta (GSK‐3β)/β‐catenin pathway in previous study. Here, to further explore the underlying mechanism and primary regulating gene, we dissected the snRNA‐seq data for the gene expression changes by iACS, finding Rgs9 as a unique downregulating gene under the ips‐iACS.…”

“…Furthermore, we also observed an augmentation in neuronal differentiation of neural stem cells by in vitro electric stimulation. 21 , 22 , 23 These preliminary studies inspired further exploration on the precise cellular and genetic mechanisms by EBS, an area of research that, to our knowledge, remains largely unexplored.…”

Impairment of hippocampal astrocyte-mediated striatal dopamine release and locomotion in Alzheimer’s disease

“…The fact that neuron and astrocyte stimulation locally induced a microglial phenotype that showed improved performance against Aβ pathology may also have important implications for strategies involving brain stimulation to reduce Aβ load and limit the disease progression [36][37][38][39][40][41] . Our results support these approaches, although they indicate that the altered connectivity of the hippocampus with other brain regions may spatially limit the effect of neuronal and astrocytic stimulation to the areas that are being directly stimulated.…”