Abstract:
: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.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Pecho-Vrieseling E,Rieker C,Fuchs S,Bleckmann D,Esposito MS,Botta P,Goldstein C,Bernhard M,Galimberti I,Müller M,Lüthi A,Arber S,Bouwmeester T,van der Putten H,Di Giorgio FPdoi
10.1038/nn.3761subject
Has Abstractpub_date
2014-08-01 00:00:00pages
1064-72issue
8eissn
1097-6256issn
1546-1726pii
nn.3761journal_volume
17pub_type
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