Cilostazol prevents amyloid β peptide_25‐35‐induced memory impairment and oxidative stress in mice

Abstract

BACKGROUND AND PURPOSECilostazol may be effective in dementia associated with a cerebral ischaemia. In this study, we examined whether it exerts beneficial effects on learning and/or memory impairment induced by Ab25-35 in mice, and compared its effects with those of aspirin. EXPERIMENTAL APPROACHAb25-35 (9 nmol) was administered to mice i.c.v. Learning and memory behaviour were evaluated by measuring spontaneous alternation in a Y-maze and a step-down type passive avoidance test, on the 5th and 8th days after injection respectively. Levels of lipid peroxidation (malondialdehyde) and cytokines in the frontal cortex and hippocampus were measured 2, 3, 5 and 7 days after the Ab25-35 injection. The effects of repeated administration of cilostazol and aspirin (both at 30 and 100 mg·kg -1 , p.o.) on any changes induced by Ab25-35 were evaluated. KEY RESULTSRepeated administration of cilostazol significantly attenuated the impairment of spontaneous alternation and the shortened step-down latency induced by Ab25-35. Aspirin did not show any beneficial effect. A significant increase in the levels of malondialdehyde (MDA) and IL-1b (only measured in hippocampus) was observed 2, 3 and 5 days after the Ab25-35 injection in the frontal cortex and hippocampus. Repeated administration of cilostazol (100 mg·kg -1 ) completely prevented the increase in MDA levels but failed to antagonize the increase in the expression of IL-1b induced by Ab25-35. CONCLUSIONS AND IMPLICATIONSThese results suggest that the protective effect of cilostazol on Ab25-35-induced memory impairment may be related to oxidative stress in the frontal cortex and the hippocampus. AbbreviationsAb, amyloid b; AD, Alzheimer's disease; APP, amyloid precursor protein; BACE, b-site of amyloid precursor protein cleaving enzyme; CMC, carboxymethyl cellulose sodium salt; CREB, cAMP-responsive element binding protein cilostazol:6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)

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