Histopathological Similarities between Scrapie and Cuprizone Toxicity in Mice

Pattison, I.H.; Jebbett, Jean N.

doi:10.1038/230115a0

Cited by 59 publications

(41 citation statements)

References 11 publications

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“…Intoxication by actinomycin D [36] copper [16] cuprizone [33], [42] ethidium bromide [50] hexachlorophene [18] isonicotinic acid hydrazide [21] lysolecithin [5] triethyltin [2] Genetic models of mitochondrial dysfunction reviewed in [43] altered proteolipid expression [3] Models of scrapie [24], [33] Veterinary pathologies of various aetiology…”

Section: Experimental Pathologies Referencementioning

confidence: 99%

Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

Szalárdy

Molnár

Török

et al. 2016

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A b s t r a c t Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM) and grey matter (GM) vacuolation in mitochondrial encephalopathies, there is a paucity of data on the exact mechanism of vacuole formation. To revisit the concepts of vacuole formation associated with mitochondrial dysfunction, we performed a comparative neuropathological analysis in Kearns-Sayre syndrome (KSS) and full-length peroxisome proliferator-activated receptor-g coactivator-1α (FL-PGC-1α)-deficient mice, a recently proposed morphological model of mitochondrial encephalopathies. Brain tissues from an individual with genetically proven KSS (22-year-old man) and aged

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Section: Experimental Pathologies Referencementioning

confidence: 99%

Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

Szalárdy

Molnár

Török

et al. 2016

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“…Prior to the discovery of the prion protein, some similarities were observed in the neuropathology associated with the toxicity of the copper chelator cuprizone and the neuropathology of scrapie (2,3). However, copper supplementation does not prevent the development of cuprizone-induced spongy degeneration, indicating that these toxic effects may not be mediated by copper chelation.…”

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confidence: 99%

Copper Chelation Delays the Onset of Prion Disease

Sigurdsson¹,

Brown

Alim³

et al. 2003

Journal of Biological Chemistry

179

152

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The prion protein (PrP) binds copper and under some conditions copper can facilitate its folding into a more protease resistant form. Hence, copper levels may influence the infectivity of the scrapie form of prion protein (PrP Sc ). To determine the feasibility of copper-targeted therapy for prion disease, we treated mice with a copper chelator, D-(؊)-penicillamine (D-PEN), starting immediately following intraperitoneal scrapie inoculation. D-PEN delayed the onset of prion disease in the mice by about 11 days (p ‫؍‬ 0.002), and reduced copper levels in brain by 29% (p < 0.01) and in blood by 22% (p ‫؍‬ 0.03) compared with control animals. Levels of other metals were not significantly altered in the blood or brain. Modest correlation was observed between incubation period and levels of copper in brain (p ‫؍‬ 0.08) or blood (p ‫؍‬ 0.04), indicating that copper levels are only one of many factors that influence the rate of progression of prion disease. In vitro, copper dose-dependently enhanced the proteinase K resistance of the prion protein, and this effect was counteracted in a dose-dependent manner by co-incubation with D-PEN. Overall, these findings indicate that copper levels can influence the conformational state of PrP, thereby enhancing its infectivity, and this effect can be attenuated by chelatorbased therapy.

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“…However, despite this clear evolutionary conservation, the normal role of PrP remains an enigma. Several possible functions have been proposed, including a role in copper homeostasis (Pattison et al, 1971;Pattison & Jebbett, 1971a;Pattison & Jebbett, 1971b;Wadsworth et al, 1999); regulation of oxidative stress through superoxide dismutase activity (Brown et al, 1999) and signal transduction (Mattei et al, 2004;Mouillet-Richard et al, 2000;Solforosi et al, 2004). As neurons express high levels of PrPC, the function of this molecule is likely to have an important role in the physiology of these cells.…”

Section: Introductionmentioning

confidence: 99%

Elevated PrPC Expression Predisposes to Increased HSV-1 Pathogenicity

Thackray

Bujdoso

2006

Antivir Chem Chemother

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PrPC is a ubiquitously expressed glycophosphatidylinositol-linked cell-surface glycoprotein found primarily in neural tissue. Although its normal function has not been established, there is evidence suggesting that PrPC is involved in cell signalling and cellular homeostasis. This suggests that variation in neuronal expression levels of this protein contributes towards pathogenicity induced by neurotropic agents. We have investigated the pathological response to infection with herpes simplex virus type-1 (HSV-1) in strains of mice that express different levels of PrPC. Prnp

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Histopathological Similarities between Scrapie and Cuprizone Toxicity in Mice

Cited by 59 publications

References 11 publications

Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

Copper Chelation Delays the Onset of Prion Disease

Elevated PrPC Expression Predisposes to Increased HSV-1 Pathogenicity

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