Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia

Naunyn Schmiedebergs Arch Pharmacol. 2010 Jun;381(6):529-39. doi: 10.1007/s00210-010-0511-z. Epub 2010 Apr 6.

Abstract

The present study was undertaken to investigate the possible mechanism of curcumin-mediated beneficial effects in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administering streptozotocin (3 mg kg(-1)) intracerebroventricularly on first and third day. Morris water maze test was employed to assess learning and memory of the animals. Biochemical analysis of brain homogenate was performed to assess brain acetyl cholinesterase (AChE) activity and total oxidative stress. Streptozotocin (STZ) produced a significant decrease in water maze performance of mice indicative of impairment in spatial reference memory. Curcumin (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits. Higher levels of brain AChE activity and oxidative stress were observed in STZ-treated animals, which were significantly attenuated by curcumin. Furthermore, the noted beneficial effect of curcumin on STZ-induced dementia was significantly abolished by pretreatment with PPAR-gamma receptor antagonist bisphenol-A-diglycidyl ether, i.e., BADGE (30 mg/kg intraperitoneally (i.p.)). It may be concluded that the beneficial effects of curcumin are mediated through the activation of PPAR-gamma receptors.

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism
  • Animals
  • Benzhydryl Compounds
  • Brain / drug effects
  • Brain / metabolism
  • Curcumin / pharmacology*
  • Dementia / drug therapy*
  • Dementia / physiopathology
  • Disease Models, Animal
  • Epoxy Compounds / pharmacology
  • Female
  • Male
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Mice
  • Oxidative Stress / drug effects
  • PPAR gamma / drug effects*
  • PPAR gamma / metabolism
  • Streptozocin

Substances

  • Benzhydryl Compounds
  • Epoxy Compounds
  • PPAR gamma
  • Streptozocin
  • Acetylcholinesterase
  • 2,2-bis(4-glycidyloxyphenyl)propane
  • Curcumin