#Ganglioside synthase knock-out reduces #prion disease #incubation time in mouse models (Am J Pathol., abstract)

[Source: American Journal of Pathology, full page: (LINK). Abstract, edited.]

Ganglioside synthase knock-out reduces prion disease incubation time in mouse models

Atsushi Kobayashi, , Zechen Qi, Taishi Shimazaki, Yoshiko Munesue, Tomomi Miyamoto, Norikazu Isoda, Hirofumi Sawa, Keisuke Aoshima, Takashi Kimura, Shirou Mohri, Tetsuyuki Kitamoto, Tadashi Yamashita, Ichiro Miyoshi

DOI: https://doi.org/10.1016/j.ajpath.2018.11.009

Accepted: November 16, 2018 – Received in revised form: November 14, 2018 – Received: September 4, 2018

 

Abstract

Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid–containing glycosphingolipids, namely gangliosides. Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft–associated proteins. To investigate the role of gangliosides in the pathogenesis of prion diseases, we performed intracerebral transmission study of a scrapie prion strain Chandler and a Gerstmann-Sträussler-Scheinker syndrome prion strain Fukuoka-1 using various knock-out mouse strains ablated with ganglioside synthase gene, ie, GD2/GM2 synthase, GD3 synthase, or GM3 synthase. Following challenge with the Chandler strain, GD2/GM2 synthase knock-out mice showed 20% reduction of incubation time, reduced prion protein deposition in the brain with attenuated glial reactions, and reduced localization of prion proteins to lipid rafts. These results raise the possibility that the gangliosides may have an important role in prion disease pathogenesis by affecting the localization of prion proteins to lipid rafts.

Funding: Supported by Grants-in-Aid for Scientific Research from JSPS (18K05963; A.K.), The Ichiro Kanehara Foundation (A.K.), The Suhara Memorial Foundation (A.K.), and The Kato Memorial Trust for Nambyo Research (A.K.).

Disclosures: None declared.

© 2018 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.

Keywords: Prions; Scrapie; Gangliosides; Animal models.

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The #EU #summary #report on #surveillance for the presence of transmissible spongiform #encephalopathies (#TSEs) in 2017 (EFSA, abstract)

[Source: European Food Safety Authority (EFSA), full page: (LINK). Abstract, edited.]

Scientific Report  / Open Access

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017

European Food Safety Authority (EFSA) / First published: 28 November 2018 / DOI:  https://doi.org/10.2903/j.efsa.2018.5492

Correspondence: zoonoses@efsa.europa.eu

Requestor: European Commission

Question number: EFSA‐Q‐2017‐00753

Acknowledgements: EFSA wishes to thank for the support provided to this scientific output to the EFSA staff members: Yves Van der Stede, Angel Ortiz Pelaez, Valentina Rizzi, Pietro Stella and Frank Boelaert, and to the EFSA contractor: Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta (Unit BEAR – Biostatistica Epidemiologia e Analisi del Rischio and staff: Giuseppe Ru, Francesco Ingravalle, Cristina Bona, Rosanna Desiato, Cristiana Maurella and Eleonora Aiassa).

Approved: 6 November 2018

 

Abstract

This report presents the results of surveillance on transmissible spongiform encephalopathies (TSEs) in bovine animals, sheep, goats, cervids and other animal species, as well as genotyping in sheep, carried out in 2017 in the European Union (EU) according to Regulation (EC) 999/2001, and in Iceland, Norway and Switzerland. In total, 1,312,714 cattle were tested by the 28 EU Member States (MSs) which is a decrease of 3% compared with 2016; 18,526 were tested by the three non‐MSs. For the first time since bovine spongiform encephalopathy (BSE) has been reported, no cases of classical BSE were reported in 2017. Six atypical BSE cases were reported by three different MSs: Spain 1 H‐BSE/2 L‐BSE; France 1 H‐BSE/1 L‐BSE; and Ireland 1 L‐BSE. Over the year, 314,547 sheep and 117,268 goats were tested in the EU. In sheep, 933 cases of scrapie were reported: 839 classical and unknown (145 index cases) by eight MSs and 94 atypical (89 index cases) by 13 MSs. Fourteen ovine scrapie cases were reported by Iceland and Norway. Of all classical scrapie cases, 98.2% occurred in sheep with genotypes of susceptible groups. The genotyping of a random sample in 21 MSs showed that 26.5% of the genotyped sheep carried genotypes of the susceptible groups. In goats 567 cases of scrapie were reported: 558 classical (42 index cases) by seven MSs and nine atypical (seven index cases) by five MSs. In total, 3,585 cervids were tested for TSE by ten MSs, mostly by Romania. All results were negative. Eleven cases of chronic wasting disease (CWD) cases were reported in cervids by Norway: nine wild reindeer, one moose and, for the first time ever, one red deer. In total, 185 animals from five species other than cattle, small ruminants and cervids were tested by three MSs, with negative results.

Keywords: Prions; TSE; Mad Cow; Scrapie; Chronic Wasting Disease; Cattle; Cervids; Sheeps; EU.

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