Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie

Bolea, Rosa; Hortells, Paloma; Martín-Burriel, Inmaculada; Vargas, Antonia; Ryffel, Bernard; Monzón, Marta; Badiola, Juan José

doi:10.1111/j.1365-2990.2010.01065.x

Cited by 8 publications

(5 citation statements)

References 75 publications

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“…Although several attempts have been made to understand the molecular events of these diseases [16], [17], [18], the precise molecular and cellular mechanisms that underlie prion disease pathogenesis, and even the role of PrP C in host species, remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Filali

Martín-Burriel

Harders³

et al. 2011

PLoS ONE

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The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.

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Section: Introductionmentioning

confidence: 99%

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Filali

Martín-Burriel

Harders³

et al. 2011

PLoS ONE

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“…Our results support findings from a previous study using mouse scrapie which demonstrated a neuroprotective effect of dietary copper depletion, but an inability to prevent neuronal death. 29 However, a balance is essential, as significant copper depletion can also have detrimental effects such as spongiosis in the brain. 40 Copper also has been shown to play a role in Alzheimer's disease (AD), a close cousin of prion diseases.…”

Section: Discussionmentioning

confidence: 99%

Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease

Nichols

Spraker

Gidlewski

et al. 2016

Prion

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Chronic wasting disease (CWD), the only known wildlife prion disease, affects deer, elk and moose. The disease is an ongoing and expanding problem in both wild and captive North American cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit disease years after initial contamination. The role of exogenous factors in CWD transmission and progression is largely unexplored. In an effort to understand the influence of environmental and dietary constituents on CWD, we collected and analyzed water and soil samples from CWD-negative and positive captive cervid facilities, as well as from wild CWD-endozootic areas. Our analysis revealed that, when compared with CWD-positive sites, CWD-negative sites had a significantly higher concentration of magnesium, and a higher magnesium/copper (Mg/Cu) ratio in the water than that from CWD-positive sites. When cevidized transgenic mice were fed a custom diet devoid of Mg and Cu and drinking water with varied Mg/Cu ratios, we found that higher Mg/Cu ratio resulted in significantly longer survival times after intracerebral CWD inoculation. We also detected reduced levels of inflammatory cytokine gene expression in mice fed a modified diet with a higher Mg/Cu ratio compared to those on a standard rodent diet. These findings indicate a role for dietary Mg and Cu in CWD pathogenesis through modulating inflammation in the brain.

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“…Additionally, at low Cu concentrations that do not affect Ctr1p, Cu also protects against Cp-induced toxicity in yeast 71. In mammalian cells, Cu and Cp increase activity of aSMase, leading to an increased production of the apoptosis inducer ceramide 97273 and both Cu and Cp-induced toxicity have also been associated with pro-apoptotic Bax 74757677787980. As we observed that ARBs cannot rescue yeast growth defects induced by noxious insults such as tunicamycin, valproic acid, acetic acid or CCCP, it seems that the protective effect of ARBs is toxin-specific.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

Spincemaille

Chandhok

Zibert

et al. 2014

MIC

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The human pathology Wilson disease (WD) is characterized by toxic copper (Cu) accumulation in brain and liver, resulting in, among other indications, mitochondrial dysfunction and apoptosis of hepatocytes. In an effort to identify novel compounds that can alleviate Cu-induced toxicity, we screened the Pharmakon 1600 repositioning library using a Cu-toxicity yeast screen. We identified 2 members of the drug class of Angiotensin II Type 1 receptor blockers (ARBs) that could increase yeast tolerance to Cu, namely Candesartan and Losartan. Subsequently, we show that specific ARBs can increase yeast tolerance to Cu and/or the chemotherapeutic agent cisplatin (Cp). The latter also induces mitochondrial dysfunction and apoptosis in mammalian cells. We further demonstrate that specific ARBs can prevent the prevalence of Cu-induced apoptotic markers in yeast, with Candesartan Cilexetil being the ARB which demonstrated most pronounced reduction of apoptosis-related markers. Next, we tested the sensitivity of a selection of yeast knockout mutants affected in detoxification of reactive oxygen species (ROS) and Cu for Candesartan Cilexetil rescue in presence of Cu. These data indicate that Candesartan Cilexetil increases yeast tolerance to Cu irrespectively of major ROS-detoxifying proteins. Finally, we show that specific ARBs can increase mammalian cell tolerance to Cu, as well as decrease the prevalence of Cu-induced apoptotic markers. All the above point to the potential of ARBs in preventing Cu-induced toxicity in yeast and mammalian cells.

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Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie

Cited by 8 publications

References 75 publications

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Gene Expression Profiling and Association with Prion-Related Lesions in the Medulla Oblongata of Symptomatic Natural Scrapie Animals

Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease

Angiotensin II type 1 receptor blockers increase tolerance of cells to copper and cisplatin

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