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BMC Neurology
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

Atorvastatin in improvement of cognitive impairments caused by amyloid β in mice: involvement of inflammatory reaction

Authors: Liandong Zhao, Tingting Chen, Chonghui Wang, Guoxi Li, Wenhui Zhi, Jun Yin, Qi Wan, Ling Chen

Published in: BMC Neurology | Issue 1/2016

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Abstract

Background

The production of inflammatory cytokines resulting from amyloid β (Aβ) is associated with the initiation of Alzheimer’s disease (AD). Atorvastatin (ATV) has been reported to improve AD, however, it is unclear how the anti-inflammatory mechanism is linked with its protection against the impairment of spatial cognitive function in AD. The present study was designed to explore what mechanism was possibly involved in the anti-inflammatory pathway in regard to the ATV treatment of AD.

Methods

We used an AD model induced by the administration of Aβ25–35 in male C57BL/6 mice and an in vitro culture system to study the protective effects of ATV on the spatial cognitive deficits, hippocampal long-term potentiation (LTP) impairment and inflammatory reaction.

Results

The intragastric administration of ATV (5 mg/kg) in Aβ25–35-treated mice significantly ameliorated the spatial cognitive deficits and prevented the LTP impairment in hippocampal CA1. The increased Iba-1 positive cells and inflammatory components in the hippocampus were reduced after the ATV treatment. The anti-inflammatory and LTP protection of ATV were abolished using the replenishment of farnesyl pyrophosphate by the administration of farnesol (FOH). The hippocampal slices culture showed Aβ25–35-induced neurotoxicity in the absence of the presence of ATV. Treatment with ATV (0.5, 1, 2.5 μmol/L) dose-dependently prevented the cell damage in hippocampus induced by Aβ25–35.

Conclusion

The administration of ATV ameliorated the cognitive deficits, depressed the inflammatory responses, improved the LTP impairment, and prevents Aβ25-35-induced neurotoxicity in cultured hippocampal neurons. These protective functions of ATV involved the pathway of reducing farnesyl pyrophosphate (FPP).
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Metadata
Title
Atorvastatin in improvement of cognitive impairments caused by amyloid β in mice: involvement of inflammatory reaction
Authors
Liandong Zhao
Tingting Chen
Chonghui Wang
Guoxi Li
Wenhui Zhi
Jun Yin
Qi Wan
Ling Chen
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0533-3

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