Atorvastatin prevents Aβ oligomer-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting Tau cleavage

Sui, Hai-juan; Zhang, Lingling; Liu, Zhou; Jin, Ying

doi:10.1038/aps.2014.161

Cited by 13 publications

(13 citation statements)

References 57 publications

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“…The neurotoxicity of Aβ has been shown in vitro [6,19] and in vivo [20,21] . Aβ, tau and their associated signaling pathways represent important therapeutic targets for AD.…”

Section: Discussionmentioning

confidence: 99%

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

et al. 2016

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Aim: A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) has shown antiapoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms. Methods: SD rats were administered IMM-H004 (8 mg·kg -1 ·d -1 , ig) or donepezil (positive control, 1 mg·kg -1 ·d -1 , ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and β-amyloid (Aβ) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. Results: OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aβ protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil. Conclusion: Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aβ pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD.

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“…The neurotoxicity of Aβ has been shown in vitro [6,19] and in vivo [20,21] . Aβ, tau and their associated signaling pathways represent important therapeutic targets for AD.…”

Section: Discussionmentioning

confidence: 99%

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

et al. 2016

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“…Alzheimer's disease (AD), which is the most common type of dementia in older people, is characterized by the abnormal accumulation of amyloid-β (Aβ) and intracellular neurofibrillary tangles (NFTs) in the brain, which results in progressive synaptic dysfunction and cognitive deficits [1][2][3][4] . An imbalance between protein production and degradation contributes to the accumulation of the proteinaceous inclusions characteristic of neurodegenerative disorders, including Aβ and tau in Alzheimer's disease 5 .…”

Section: Introductionmentioning

confidence: 99%

Intraperitoneal injection of IFN-γ restores microglial autophagy, promotes amyloid-β clearance and improves cognition in APP/PS1 mice

Yang

Xing

et al. 2020

Cell Death Dis

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Autophagy is a major self-degradative process that maintains cellular homeostasis and function in mammalian cells. Autophagic dysfunction occurs in the early pathogenesis of Alzheimer's disease (AD) and directly regulates amyloid-β (Aβ) metabolism. Although it has been proven that the cytokine IFN-γ enhances autophagy in macrophage cell lines, whether the signaling cascade is implicated in Aβ degradation in AD mouse models remains to be elucidated. Here, we found that 9 days of the intraperitoneal administration of IFN-γ significantly increased the LC3II/I ratio and decreased the level of p62 in APP/PS1 mice, an AD mouse model. In vitro, IFN-γ protected BV2 cells from Aβ toxicity by upregulating the expressions of Atg7 and Atg5 and the LC3II/I ratio, whereas these protective effects were ablated by interference with Atg5 expression. Moreover, IFN-γ enhanced autophagic flux, probably through suppressing the AKT/ mTOR pathway both in vivo and in vitro. Importantly, using intravital two-photon microscopy and fluorescence staining, we found that microglia interacted with exogenous IFN-γ and Aβ, and surrounded Aβ in APP/PS1;CX3CR1-GFP +/− mice. In addition, IFN-γ treatment decreased the Aβ plaque load in the cortex and hippocampus and rescued cognitive deficits in APP/PS1 mice. Our data suggest a possible mechanism by which the peripheral injection of IFN-γ restores microglial autophagy to induce the phagocytosis of cerebral Aβ, which represents a potential therapeutic approach for the use of exogenous IFN-γ in AD.

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“…Hippocampal slice cultures were prepared according to the previously reported method [ 20 ]. Briefly, mice were decapitated 15 days after Aβ25-35 administration.…”

Section: Methodsmentioning

confidence: 99%

“…The animals without Aβ25-35 administration were decapitated. Hippocampal slice cultures were prepared as reported previously [ 20 ]. To examine the dose-dependent protective effects of ATV, different doses at 0.5, 1 and 2.5 μmol/L in the culture medium were used.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2016

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BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionThe 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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Atorvastatin prevents Aβ oligomer-induced neurotoxicity in cultured rat hippocampal neurons by inhibiting Tau cleavage

Cited by 13 publications

References 57 publications

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats

Intraperitoneal injection of IFN-γ restores microglial autophagy, promotes amyloid-β clearance and improves cognition in APP/PS1 mice

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

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