Combined Adult Neurogenesis and BDNF Mimic Exercise Effects on Cognition in an Alzheimer's Mouse Model

Science. 2018 Sep 7;361(6406):eaan8821. doi: 10.1126/science.aan8821.

Abstract

Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's disease (AD) pathology. We found that exercise provided cognitive benefit to 5×FAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain-derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor exercise, in the absence of increased AHN, ameliorated cognition. We successfully mimicked the beneficial effects of exercise on AD mice by genetically and pharmacologically inducing AHN in combination with elevating BDNF levels. Suppressing AHN later led to worsened cognitive performance and loss of preexisting dentate neurons. Thus, pharmacological mimetics of exercise, enhancing AHN and elevating BDNF levels, may improve cognition in AD. Furthermore, applied at early stages of AD, these mimetics may protect against subsequent neuronal cell death.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology*
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Carbazoles / administration & dosage
  • Carbazoles / pharmacology
  • Cell Death
  • Cognition*
  • Disease Models, Animal
  • Exercise*
  • Female
  • Fibronectins
  • Hippocampus / cytology*
  • Humans
  • Interleukin-6 / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Neurogenesis* / drug effects
  • Physical Conditioning, Animal
  • Wnt3 Protein / genetics

Substances

  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Brain-Derived Neurotrophic Factor
  • Carbazoles
  • FNDC5 protein, human
  • Fibronectins
  • Interleukin-6
  • P7C3 compound
  • Wnt3 Protein
  • Wnt3 protein, mouse
  • interleukin-6, mouse