Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia
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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 administrating 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-γ 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-γ receptors.
KeywordsCurcumin Streptozotocin Dementia Alzheimer Morris water maze
The authors would like to acknowledge Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala for providing technical facilities.
- Baum L, Alex NG (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimer’s Dis 6:367–377Google Scholar
- Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA (2008) Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther 326(1):196–208CrossRefPubMedGoogle Scholar
- De la Monte SM, Tong M, Lester-Coll N, Plater M Jr, Wands JR (2006) Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. J Alzheimer’s disease 10(1):89–109Google Scholar
- Fukui K, Omoi NO, Hayasaka T, Shinnkai T, Suzuki S, Abe K (2002) Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by Vitamin E. Ann N Y Acad Sci 959:272–284Google Scholar
- Hoyer S, Muller D, Plaschke K (1994) Desensitization of brain insulin receptor: effect on glucose energy and related metabolism. J Neural Transmission 44(Suppl):259–268Google Scholar
- Ishida H, Takizawa M, Ozawa S, Nakamichi Y, Yamaguchi S, Katsuta NS (2004) Pioglitazone improves insulin secreatory capacity and prevents the loss of beta-cell mass in obese diabetic db/db mice: possible protection of beta cells from oxidative stress. Metabolism 53(4):488–494CrossRefPubMedGoogle Scholar
- Juraj C (2007) PPAR-γ: therapeutic target for ischemic stroke. Trends Pharmacol Sci 28:243–249Google Scholar
- Parle M, Singh N (2004) Animal models for testing memory. Asia Pacific J Pharmacol 16:101–120Google Scholar
- Thomas D, Michael TH, Magdalena S, Jhonnes D, Jorg BS (2004) Protection by Pioglitazone in the MPTP model of Parkinson’s disease correlates with IkB induction and block of NFkB and INOS activation. J Neurochem 88:494–501Google Scholar
- Voss G, Sachsse K (1970) Red cell and plasma cholinesterase activities in microsamples of human and animal blood determined simultaneously by a modified acetylthiocholine-DTNB procedure. Toxicol Appl Pharmacol 16:764–772Google Scholar