Quercetin promotes learning and memory performance concomitantly with neural stem/progenitor cell proliferation and neurogenesis in the adult rat dentate gyrus

Int J Dev Neurosci. 2019 May:74:18-26. doi: 10.1016/j.ijdevneu.2019.02.005. Epub 2019 Feb 26.

Abstract

The decline in neurogenesis is a very critical problem in Alzheimer disease. Different biological activities have been reported for medicinal application of quercetin. Herein, we investigated the neurogenesis potential of quercetin in a rat model of Alzheimer's disease induced by amyloid-beta injection. Rats were randomly divided into Control, Alzheimer + Saline and Alzheimer + Quercetin groups. Following the administration of Amyloid-beta, rats in the Alzheimer + Quercetin group received 40 mg/kg/day quercetin orally for one month. Our data demonstrated amyloid-β injection could impair learning and memory processing in rats indicated by passive avoidance test evaluation. We noted that one-month quercetin treatment alleviated the detrimental effects of amyloid-β on spatial learning and memory parameters using Morris water maze analysis. Quercetin was found to increase the number of proliferating neural stem/progenitor cells. Notably, quercetin increased the number of DCX-expressing cells, indicating the active dynamic growth of neural progenitor cells in the dentate gyrus of the hippocampus. We further observed that the quercetin improved the number of BrdU/NeuN positive cells contributed to enhanced adult neurogenesis. Based on our results, quercetin had the potential to promote the expression of BDNF, NGF, CREB, and EGR-1 genes involved in regulating neurogenesis. These data suggest that quercetin can play a valuable role in alleviating Alzheimer's disease symptoms by enhancing adult neurogenesis mechanism.

Keywords: Alzheimer’s disease; Cell proliferation; Learning and memory; Neural stem/progenitor cells; Neurogenesis; Quercetin.

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / complications
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Antioxidants / therapeutic use*
  • Avoidance Learning / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • CREB-Binding Protein / metabolism
  • Cell Proliferation / drug effects*
  • Dentate Gyrus / drug effects
  • Dentate Gyrus / pathology*
  • Disease Models, Animal
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Early Growth Response Protein 1 / metabolism
  • Learning Disabilities / drug therapy*
  • Learning Disabilities / etiology
  • Male
  • Maze Learning / drug effects
  • Microtubule-Associated Proteins / metabolism
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / physiology*
  • Neurogenesis / drug effects*
  • Neuropeptides / metabolism
  • Peptide Fragments / toxicity
  • Quercetin / therapeutic use*
  • Rats
  • Rats, Wistar

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Dcx protein, rat
  • Doublecortin Domain Proteins
  • Doublecortin Protein
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Microtubule-Associated Proteins
  • Neuropeptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Quercetin
  • CREB-Binding Protein