Photobiomodulation Using a Low-Level Light-Emitting Diode Improves Cognitive Dysfunction in the 5XFAD Mouse Model of Alzheimer's Disease

J Gerontol A Biol Sci Med Sci. 2020 Mar 9;75(4):631-639. doi: 10.1093/gerona/gly240.

Abstract

Photobiomodulation using low-level light-emitting diode can be rapidly applied in neurological and physiological disorders safely and noninvasively. Photobiomodulation is effective for chronic diseases because of fewer side effects than drugs. Here we investigated the effects of photobiomodulation using light-emitting diode on amyloid plaques, gliosis, and neuronal loss to prevent and/or recover cognitive impairment, and optimal timing of photobiomodulation initiation for recovering cognitive function in a mouse model of Alzheimer's disease. 5XFAD mice were used as an Alzheimer's disease model. Animals receiving photobiomodulation treatment were divided into two groups: an early group starting photobiomodulation at 2 months of age (5XFAD+Early), and a late group starting photobiomodulation at 6 months of age (5XFAD+Delay). Both groups received photobiomodulation 20 minutes per session three times per week for 14 weeks. The Morris water maze, passive avoidance, and elevated plus maze tests were performed at 10 months of age. Immunohistochemistry and Western blot were performed after behavioral evaluation. The results showed that photobiomodulation treatment at early stages reduced amyloid accumulation, neuronal loss, and microgliosis and alleviated the cognitive dysfunction in 5XFAD mice, possibly by increasing insulin degrading enzyme related to amyloid-beta degradation. Photobiomodulation may be an excellent candidate for advanced preclinical Alzheimer's disease research.

Keywords: Amyloid-β; Gliosis; LED therapy; Neuronal cell death; Photostimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alzheimer Disease / genetics
  • Alzheimer Disease / psychology
  • Alzheimer Disease / radiotherapy*
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Avoidance Learning / radiation effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebral Cortex / radiation effects
  • Cognition / radiation effects
  • Disease Models, Animal
  • Gliosis / pathology
  • Gliosis / prevention & control
  • Humans
  • Lasers, Semiconductor / therapeutic use
  • Low-Level Light Therapy*
  • Male
  • Maze Learning / radiation effects
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Microglia / pathology
  • Microglia / radiation effects
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutation, Missense
  • Proteolysis / radiation effects

Substances

  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Mutant Proteins