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Cilostazol prevents amyloid β peptide 25‐35 ‐induced memory impairment and oxidative stress in mice
Author(s) -
Hiramatsu Masayuki,
Takiguchi Osanao,
Nishiyama Aki,
Mori Hiromasa
Publication year - 2010
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2010.01014.x
Subject(s) - cilostazol , malondialdehyde , hippocampus , lipid peroxidation , medicine , spontaneous alternation , memory impairment , oxidative stress , aspirin , endocrinology , pharmacology , anesthesia , chemistry , cognition , psychiatry
BACKGROUND AND PURPOSE Cilostazol 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 Aβ 25‐35 in mice, and compared its effects with those of aspirin. EXPERIMENTAL APPROACH Aβ 25‐35 (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 Aβ 25‐35 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 Aβ 25‐35 were evaluated. KEY RESULTS Repeated administration of cilostazol significantly attenuated the impairment of spontaneous alternation and the shortened step‐down latency induced by Aβ 25‐35 . Aspirin did not show any beneficial effect. A significant increase in the levels of malondialdehyde (MDA) and IL‐1β (only measured in hippocampus) was observed 2, 3 and 5 days after the Aβ 25‐35 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‐1β induced by Aβ 25‐35 . CONCLUSIONS AND IMPLICATIONS These results suggest that the protective effect of cilostazol on Aβ 25‐35 ‐induced memory impairment may be related to oxidative stress in the frontal cortex and the hippocampus.