title: Non-cell autonomous cell death caused by transmission of Huntingtin aggregates in Drosophila.
abstract: Recent evidence indicates that protein aggregates can spread between neurons in several neurodegenerative diseases but much remains unknown regarding the underlying mechanisms responsible for this spreading and its role in disease progression. We recently demonstrated that mutant Huntingtin aggregates spread between cells within the Drosophila brain resulting in non-cell autonomous loss of a pair of large neurons in the posterior protocerebrum. However, the full extent of neuronal loss throughout the brain was not determined. Here we examine the effects of driving expression of mutant Huntingtin in Olfactory Receptor Neurons (ORNs) by using a marker for cleaved caspase activity to monitor neuronal apoptosis as a function of age. We find widespread caspase activity in various brain regions over time, demonstrating that non-cell autonomous damage is widespread. Improved understanding of which neurons are most vulnerable and why should be useful in developing treatment strategies for neurodegenerative diseases that involve transcellular spreading of aggregates.
authors.affiliation: a Laboratory of Genetics, University of Wisconsin , Madison , WI , USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Babcock
authors.affiliation: a Laboratory of Genetics, University of Wisconsin , Madison , WI , USA.
authors.forename: Barry
authors.initials: B
authors.lastname: Ganetzky
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000166:cytology / Q000378:metabolism; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism* / Q000648:ultrastructure; D029721:Drosophila Proteins / Q000032:analysis / Q000378:metabolism; D000071058:Huntingtin Protein / Q000378:metabolism*; D009410:Nerve Degeneration; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism; D066329:Protein Aggregates
chemical_list: D029721:Drosophila Proteins; C542005:Htt protein, Drosophila; D000071058:Huntingtin Protein; D066329:Protein Aggregates; D020169:Caspases; C103568:Dcp-1 protein, Drosophila
keywords: aggregate spreading; apoptosis; cell death; drosophila; huntington's disease; neurodegeneration