Dataset Information

Cilostazol prevents amyloid ? peptide(25-35)-induced memory impairment and oxidative stress in mice.

ABSTRACT:

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 A?(25-35) in mice, and compared its effects with those of aspirin.

Experimental approach

A?(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 A?(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 A?(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 A?(25-35) . Aspirin did not show any beneficial effect. A significant increase in the levels of malondialdehyde (MDA) and IL-1? (only measured in hippocampus) was observed 2, 3 and 5 days after the A?(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-1? induced by A?(25-35).

Conclusions and implications

These results suggest that the protective effect of cilostazol on A?(25-35)-induced memory impairment may be related to oxidative stress in the frontal cortex and the hippocampus.

SUBMITTER: Hiramatsu M

PROVIDER: S-EPMC3010591 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cilostazol prevents amyloid β peptide(25-35)-induced memory impairment and oxidative stress in mice.

Hiramatsu Masayuki M Takiguchi Osanao O Nishiyama Aki A Mori Hiromasa H

British journal of pharmacology 20101201 8

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>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 ...[more]

PMID: 20825411

Similar Datasets

Project description:BackgroundWe previously hypothesized that achievement of recovery of brain function after the injury requires the reconstruction of neuronal networks, including neurite regeneration and synapse reformation. Kihi-to is composed of twelve crude drugs, some of which have already been shown to possess neurite extension properties in our previous studies. The effect of Kihi-to on memory deficit has not been examined. Thus, the goal of the present study is to determine the in vivo and in vitro effects of Kihi-to on memory, neurite growth and synapse reconstruction.MethodsEffects of Kihi-to, a traditional Japanese-Chinese traditional medicine, on memory deficits and losses of neurites and synapses were examined using Alzheimer's disease model mice. Improvements of Abeta(25-35)-induced neuritic atrophy by Kihi-to and the mechanism were investigated in cultured cortical neurons.ResultsAdministration of Kihi-to for consecutive 3 days resulted in marked improvements of Abeta(25-35)-induced impairments in memory acquisition, memory retention, and object recognition memory in mice. Immunohistochemical comparisons suggested that Kihi-to attenuated neuritic, synaptic and myelin losses in the cerebral cortex, hippocampus and striatum. Kihi-to also attenuated the calpain increase in the cerebral cortex and hippocampus. When Kihi-to was added to cells 4 days after Abeta(25-35) treatment, axonal and dendritic outgrowths in cultured cortical neurons were restored as demonstrated by extended lengths of phosphorylated neurofilament-H (P-NF-H) and microtubule-associated protein (MAP)2-positive neurites. Abeta(25-35)-induced cell death in cortical culture was also markedly inhibited by Kihi-to. Since NF-H, MAP2 and myelin basic protein (MBP) are substrates of calpain, and calpain is known to be involved in Abeta-induced axonal atrophy, expression levels of calpain and calpastatin were measured. Treatment with Kihi-to inhibited the Abeta(25-35)-evoked increase in the calpain level and decrease in the calpastatin level. In addition, Kihi-to inhibited Abeta(25-35)-induced calcium entry.ConclusionIn conclusion Kihi-to clearly improved the memory impairment and losses of neurites and synapses.