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Sainte-Foy-lès-Lyon, France

Langeveld J.P.M.,Central Veterinary Institute part of Wageningen UR | Jacobs J.G.,Central Veterinary Institute part of Wageningen UR | Erkens J.H.F.,Central Veterinary Institute part of Wageningen UR | Baron T.,Neurodegenerative Diseases Unit | And 8 more authors.
Prion | Year: 2014

Efforts to differentiate bovine spongiform encephalopathy (BSE) from scrapie in prion infected sheep have resulted in effective methods to decide about the absence of BSE. In rare instances uncertainties remain due to assumptions that BSE, classical scrapie and CH1641 - a rare scrapie variant-could occur as mixtures. In field samples including those from fallen stock, triplex Western blotting analyses of variations in the molecular properties of the proteinase K resistant part of the disease-associated form of prion protein (PrPres) represents a powerful tool for quick discrimination purposes. In this study we examined 7 deviant ovine field cases of scrapie for some typical molecular aspects of PrPres found in CH1641-scrapie, classical scrapie and BSE. One case was most close to scrapie with respect to molecular mass of its non-glycosylated fraction and N-terminally located 12B2-epitope content. Two cases were unlike classical scrapie but too weak to differentiate between BSE or CH1641. The other 4 cases appeared intermediate between scrapie and CH1641 with a reduced molecular mass and 12B2-epitope content, together with the characteristic presence of a second PrPres population. The existence of these 2 PrPres populations was further confirmed through deglycosylation by PNGaseF. The findings indicate that discriminatory diagnosis between classical scrapie, CH1641 and BSE can remain inconclusive with current biochemical methods. Whether such intermediate cases represent mixtures of TSE strains should be further investigated e.g. in bioassays with rodent lines that are varying in their susceptibility or other techniques suitable for strain typing. © 2014 Taylor & Francis Group, LLC. Source


Levigoureux E.,University Claude Bernard Lyon 1 | Lancelot S.,University Claude Bernard Lyon 1 | Bouillot C.,CERMEP Imagerie du Vivant | Chauveau F.,University Claude Bernard Lyon 1 | And 5 more authors.
Current Alzheimer Research | Year: 2014

Alpha-synuclein (_-syn) aggregation is a neuropathological hallmark of many neurodegenerative diseases, collectively termed synucleinopathies. There is currently no pre-mortem diagnosis tool for these diseases. Although some compounds have been described as potential ligands for _-syn aggregates, no specific PET radiotracer of aggregated _-syn is currently available. Recently, [18F]BF227 has been proposed as an _-syn PET radiotracer in the absence of other specific candidates. We proposed here, for the first time, to use this radiotracer in an accelerated mouse model of synucleinopathy presenting _-syn depositions in brainstem and thalamus. Our in vivo and in vitro studies showed that [18F]BF227 does not bind to _-syn aggregates. These results highlight the fact that [18F]BF227 PET has no suitable characteristics for monitoring this experimental synucleinopathy, justifying the need to develop alternative _-syn PET radiotracers. © 2014 Bentham Science Publishers. Source


Vulin J.,Neurodegenerative Diseases Unit | Beck K.E.,Veterinary Laboratories Agency Weybridge | Bencsik A.,Neurodegenerative Diseases Unit | Lakhdar L.,Neurodegenerative Diseases Unit | And 2 more authors.
Journal of Neuropathology and Experimental Neurology | Year: 2012

A few cases of transmissible spongiform encephalopathies in sheep have been described in France in which the protease-resistant prion protein (PrP res) exhibited some features in Western blot of experimental bovine spongiform encephalopathy in sheep. Their molecular characteristics were indistinguishable from those produced in the CH1641 experimental scrapie isolate. Four of these CH1641-like isolates were inoculated intracerebrally into wild-type C57Bl/6 mice. In striking contrast to previous results in ovine transgenic mice, CH1641 transmission in wild-type mice was efficient. Several components of the strain signature, that is, PrP res profile, brain distribution, and morphology of the deposits of the disease-associated prion protein, had some similarities with "classical" scrapie and clearly differed from both bovine spongiform encephalopathy in sheep and CH1641 transmission in ovine transgenic mice. These results on CH1641-like isolates in wild-type mice may be consistent with the presence in these isolates of mixed conformers with different abilities to propagate and mediate specific disease phenotypes in different species. © 2012 by the American Association of Neuropathologists, Inc. Source


Chorfa A.,Neurodegenerative Diseases Unit | Lazizzera C.,Neurodegenerative Diseases Unit | Betemps D.,Neurodegenerative Diseases Unit | Morignat E.,Neurodegenerative Diseases Unit | And 3 more authors.
Archives of Toxicology | Year: 2014

The etiology of most human neurodegenerative disorders is believed to be multifactorial and consists of an interaction between environmental factors and genetic predisposition. Regarding Parkinson’s disease (PD), the second most frequent neurodegenerative disease characterized by the aggregation of the alpha-synuclein (αS) protein, numerous epidemiological and experimental studies suggested a possible role of exposure to some pesticides. Whereas epidemiological studies largely failed to identify pesticides specifically involved in PD, it is of critical importance to set up in vitro toxicity studies of pesticides. We measured changes of αS levels following pesticide exposures of human cell lines in vitro, using either ELISA detection of endogenous αS or flow cytometry after overexpression using recombinant adenoviruses. We showed that three pesticides (paraquat, rotenone and maneb), which have frequently been associated with PD, produced a dose-dependent increase in cellular αS levels, but also of αS released into the culture medium. Examining an additional series of 20 pesticides from different families and chemical structures, we found that beside some insecticides, including an organophosphate and three pyrethroids, a majority of the 12 studied fungicides were also producing an αS accumulation, three of them (thiophanate-methyl, fenhexamid and cyprodinil) having similar or more pronounced effects than paraquat. A variety of pesticides can disrupt αS homeostasis in vitro; our data illustrate an experimental strategy that could help in the identification of chemicals that could be specifically involved in PD etiology. © 2014 Springer-Verlag Berlin Heidelberg Source

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