Effects of electroacupuncture on DNA methylation of the TREM2 gene in senescence-accelerated mouse prone 8 mice

Acupunct Med. 2022 Oct;40(5):463-469. doi: 10.1177/09645284221077103. Epub 2022 Mar 2.

Abstract

Objective: To explore the mechanism by which electroacupuncture (EA) upregulates triggering receptor expressed on myeloid cells 2 (TREM2) protein in the hippocampus of Alzheimer's disease (AD) model animals from the perspective of TREM2 DNA methylation.

Methods: In total, 24 eight-month-old senescence-accelerated mouse prone 8 (SAMP8) mice were divided into an (untreated) AD group (n = 8), donepezil group (receiving donepezil treatment, n = 8) or EA group (receiving an EA intervention, n = 8). A healthy control group comprising 8-month-old senescence-accelerated mouse resistant 1 (SAMR1) mice (n = 8) was also included. Western blotting, bisulfite sequencing, and oxidative bisulfite sequencing were applied to test the relative expression of TREM2 protein and the methylation levels of the TREM2 gene.

Results: EA significantly upregulated the relative expression of TREM2 protein (p < 0.01), downregulated the 5-methylcytosine level (p < 0.01) and upregulated the 5-hydroxymethylcytosine level (p < 0.05) in the hippocampus.

Conclusion: Downregulation of 5-methylcytosine levels and upregulation of 5-hydroxymethylcytosine levels in the TREM2 gene might be the mechanism by which EA promotes the expression of TREM2 protein.

Keywords: Alzheimer’s disease; donepezil; electroacupuncture; senescence-accelerated mouse prone 8; triggering receptor expressed on myeloid cells 2.

MeSH terms

  • 5-Methylcytosine / metabolism
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / therapy
  • Animals
  • DNA Methylation / genetics
  • Disease Models, Animal
  • Donepezil
  • Electroacupuncture*
  • Hippocampus / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism

Substances

  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Trem2 protein, mouse
  • 5-Methylcytosine
  • Donepezil