Drosophila clock neurons as a model to explore the selective vulnerability to huntingtin polyglutamine elongation

NARA I MURARO; ANA RICCIUTI

Congreso virtual debido a pandemia de COVID19

Congreso; XXXV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2020

Sociedad Argentina de Investigación en Neurociencias

One of the hallmarks of polyglutamine (polyQ) diseases is the selective vulnerability of different neurons in spite of ubiquitous expression of the pathogenic protein. The reasons behind this specificity underlying neurodegeneration is still an unsolved mystery. It has been reported that the two circadian clusters of lateral ventral neurons (LNv) of Drosophila melanogaster respond differently to the elongation of the polyQ tract of huntingtin (Htt) protein. It has been shown that while HttpolyQ protein functionally ablates the small LNvs (sLNvs) subgroup, the large LNvs (lLNV) remain unaltered. Our goal is to explore this differential response of LNvs to the HttpolyQ. In order to do this, we are taking two different experimental approaches: overexpressing the human track of huntingtin polyQ protein in LNvs and downregulating the fly endogenous huntingtin protein in these same clusters. In each of these different paradigmes, we are studying morphological phenotypes and the consequences over the behaviors these neurons command.Here we show preliminary data suggesting that downregulation of the fly endogenous huntingtin with dHttRNAi expression in LNvs impairs circadian rhythmicity and affects sleep behaviour. Also, we will share results that question the lLNvs immunity to HttpolyQ, since we find that lLNvs of aged flies display HttpolyQ protein aggregation, both in their somas and on axonal projections.