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

Qian Liu; Adam Contreras; Muhammad Shan Afaq; Weijian Yang; Daniel K Hsu; Michael Russell; Bruce Lyeth; Theodore P Zanto; Min Zhao

doi:10.1186/s13578-023-01085-5

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

Cell Biosci. 2023 Jul 28;13(1):138. doi: 10.1186/s13578-023-01085-5.

Authors

Qian Liu^{1

2}, Adam Contreras¹, Muhammad Shan Afaq¹, Weijian Yang³, Daniel K Hsu¹, Michael Russell¹, Bruce Lyeth⁴, Theodore P Zanto⁵, Min Zhao⁶

Affiliations

¹ Institute for Regenerative Cures, Department of Ophthalmology & Vision Science, Department of Dermatology, University of California Davis, Sacramento, CA, 95817, USA.
² Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology (SIAT), Chinese Academy of Sciences, Shenzhen, China.
³ Department of Electrical and Computer Engineering, University of California, Davis, CA, 95616, USA.
⁴ Department of Neurological Surgery, University of California, Davis, CA, 95616, USA.
⁵ Neuroscape, Department of Neurology, University of California San Francisco, San Francisco, CA, 94158, USA. Theodore.Zanto@ucsf.edu.
⁶ Institute for Regenerative Cures, Department of Ophthalmology & Vision Science, Department of Dermatology, University of California Davis, Sacramento, CA, 95817, USA. minzhao@ucdavis.edu.

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.

Keywords: 5xFAD mouse; Alternating current stimulation; Alzheimer’s disease; Aβ; Beta amyloid; Gamma wave; Learning and memory; Microglia.

Abstract

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