Impaired hippocampal neurogenesis and its enhancement with ghrelin in 5XFAD mice

J Alzheimers Dis. 2014;41(1):233-41. doi: 10.3233/JAD-132417.


Alzheimer's disease (AD) is an age-related neurological disorder characterized by the deposition of amyloid-β (Aβ), cognitive deficits, and neuronal loss. The decline in neurogenic capacity could participate in neuronal vulnerability and contribute to memory impairment in AD. In our longitudinal study with AD model mice (5XFAD mice), we found that the number of doublecortin (neurogenesis marker)-positive cells in 5XFAD mice was significantly decreased compared to wild-type littermate mice. Using Aβ immunostaining with 4G8 antibody, we observed that impairment in neurogenesis might be associated with the deposits of amyloid plaques. To investigate the effect of the neurogenic hormone ghrelin on defective neurogenesis in the AD brain, 5XFAD mice were administered peripherally with ghrelin. We found that treatment with ghrelin increased the number of doublecortin, HH3, and calretinin-stained cells in the hippocampus of 5XFAD mice. In 5XFAD mice treated with ghrelin, the 4G8-positive area was not significantly different from the saline-treated 5XFAD mice. Together, these findings suggest that hippocampal neurogenesis is impaired in 5XFAD mice and that treatment with ghrelin successfully rescued the abnormality of neurogenesis in 5XFAD mice without affecting Aβ pathology.

Keywords: 5XFAD mice; Alzheimer's disease; adult neurogenesis; amyloid plaque; ghrelin; hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / pathology
  • Dentate Gyrus / physiopathology
  • Disease Models, Animal
  • Ghrelin / pharmacology*
  • Gliosis / drug therapy
  • Gliosis / pathology
  • Gliosis / physiopathology
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Humans
  • Longitudinal Studies
  • Male
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / physiology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neuroprotective Agents / pharmacology*
  • Plaque, Amyloid / drug therapy
  • Plaque, Amyloid / pathology
  • Plaque, Amyloid / physiopathology


  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Ghrelin
  • Neuroprotective Agents