Activation of brain glucose metabolism ameliorating cognitive impairment in APP/PS1 transgenic mice by electroacupuncture

Free Radic Biol Med. 2017 Nov;112:174-190. doi: 10.1016/j.freeradbiomed.2017.07.024. Epub 2017 Jul 26.


An essential feature of Alzheimer's disease (AD) is implicated in brain energy metabolic impairment that is considered underlying pathogenesis of cognitive impairment. Therefore, therapeutic interventions to allay cognitive deficits that target energy metabolism may be an efficacy strategy in AD. In this study, we found that electroacupuncture (EA) at the DU20 acupoint obviously increased glucose metabolism in specific brain regions such as cortex, hippocampus, cingulate gyrus, basal forebrain septum, brain stem, and cerebellum in APP/PS1 transgenic mice by animal 18F-Fluoro-2-deoxy-D-Glucose (18F-FDG)/positron emission tomography (PET) imaging, accompanied by cognitive improvements in the spatial reference learning and memory and memory flexibility and novel object recognition performances. Further evidence shown energy metabolism occurred in neurons or non-neuronal cells of the cortex and hippocampus in terms of the co-location of GLUT3/NeuN and GLUT1/GFAP. Simultaneously, metabolic homeostatic factors were critical for glucose metabolism, including phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and AKT serine/threonine kinase. Furthermore, EA-induced phosphorylated AMPK and AKT inhibited the phosphorylation level of the mammalian target of rapamycin (mTOR) to decrease the accumulation of amyloid-beta (Aβ) in the cortex and hippocampus. These findings are concluded that EA is a potential therapeutic target for delaying memory decline and Aβ deposition of AD. The AMPK and AKT are implicated in the EA-induced cortical and hippocampal energy metabolism, which served as a contributor to improving cognitive function and Aβ deposition in a transgenic mouse model of AD.

Keywords: (18)F-Fluoro-2-deoxy-D-Glucose; AKT; Adenosine monophosphate-activated protein kinase; Alzheimer's disease; Cognitive impairment; Electroacupuncture; Glucose metabolism.

MeSH terms

  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / pathology
  • Cognitive Dysfunction / therapy*
  • DNA-Binding Proteins
  • Electroacupuncture / methods*
  • Energy Metabolism / genetics
  • Exploratory Behavior
  • Fluorodeoxyglucose F18 / administration & dosage
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / genetics
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / genetics
  • Glucose Transporter Type 3 / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Humans
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Positron-Emission Tomography
  • Spatial Learning


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • DNA-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Nerve Tissue Proteins
  • NeuN protein, mouse
  • Nuclear Proteins
  • Slc2a1 protein, mouse
  • Slc2a3 protein, mouse
  • glial fibrillary astrocytic protein, mouse
  • Fluorodeoxyglucose F18
  • Glucose