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

NARA MURARO; ANA RICCIUTI

Villa Carlos Paz, Córdoba

Congreso; XXXIV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019

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 studying morphological phenotypes and the consequences over the behaviors these neurons command. Our preliminary results regarding the morphology of the LNvs under the expression of HttpolyQ in young flies fit well with the published literature. We have found that, in spite of being expressed in both neuronal types, sLNvs present protein accumulations of HttpolyQ and lLNvs do not. However, in aged flies lLNvs also show HttpolyQ protein aggregation, both in the somas and on their projections. These results suggest that, although the reported differential sensibility between the two neuronal groups exists, lLNvs are not immune to HttpolyQ protein aggregation. We will also show preliminary data regarding the effect of downregulating the fly endogenous huntingtin in LNvs. dHttRNAi expression in LNvs impairs circadian rhythmicity and affects sleep behaviour.