Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling

J Med Food. 2014 Jun;17(6):641-9. doi: 10.1089/jmf.2013.2965. Epub 2014 Apr 8.


Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.

Keywords: CREB; Curcuma longa; D-galactose; brain-derived neurotrophic factor; subgranular zone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Animals
  • Brain / cytology
  • Brain / drug effects*
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • CREB-Binding Protein / metabolism
  • Cell Proliferation / drug effects
  • Cognition Disorders / chemically induced
  • Cognition Disorders / drug therapy*
  • Cognition Disorders / metabolism
  • Curcuma / chemistry
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Galactose
  • Male
  • Maze Learning / drug effects*
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Mice, Inbred C57BL
  • Models, Animal
  • Neurogenesis / drug effects*
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Signal Transduction
  • Spatial Memory / drug effects*
  • Up-Regulation


  • Brain-Derived Neurotrophic Factor
  • Plant Extracts
  • CREB-Binding Protein
  • Crebbp protein, mouse
  • Curcumin
  • Galactose