Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons

Pecho-Vrieseling, Eline and Rieker, Claus and Fuchs, Sascha and Bleckmann, Dorothee and Esposito, Maria Soledad and Botta, Paolo and Goldstein, Chris and Bernhard, Mario and Galimberti, Ivan and Müller, Matthias and Lüthi, Andreas and Arber, Silvia and Bouwmeester, Tewis and van der Putten, Herman and Di Giorgio, Francesco Paolo. (2014) Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons. Nature neuroscience, Vol. 17, H. 8. pp. 1064-1072.

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Official URL: http://edoc.unibas.ch/dok/A6289231

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In Huntington's disease (HD), whether transneuronal spreading of mutant huntingtin (mHTT) occurs and its contribution to non-cell autonomous damage in brain networks is largely unknown. We found mHTT spreading in three different neural network models: human neurons integrated in the neural network of organotypic brain slices of HD mouse model, an ex vivo corticostriatal slice model and the corticostriatal pathway in vivo. Transneuronal propagation of mHTT was blocked by two different botulinum neurotoxins, each known for specifically inactivating a single critical component of the synaptic vesicle fusion machinery. Moreover, healthy human neurons in HD mouse model brain slices displayed non-cell autonomous changes in morphological integrity that were more pronounced when these neurons bore mHTT aggregates. Altogether, our findings suggest that transneuronal propagation of mHTT might be an important and underestimated contributor to the pathophysiology of HD.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
09 Associated Institutions > Friedrich Miescher Institut FMI
UniBasel Contributors:Arber, Silvia and Esposito, Maria Soledad
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature America
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Oct 2014 09:19
Deposited On:10 Oct 2014 09:19

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