Contributions of neurons and astrocytes together with metabolic alterations in new cell-type specific mouse models of Huntington’s disease.

Huntington’s disease (HD) is a rare neurodegenerative disease caused by mutation on the gene coding for the huntingtin protein (HTT). Despite ubiquitous expression of the mutant HTT, a selective vulnerability of GABAergic medium sized spiny neurons (MSNs) of the striatum is observed. Additionally to these alterations, recent data have suggested the contribution of non-neuronal cells, in particular astrocytes, to physiopathology.

Our strategy consists to model the disease using cell-type specific viral vectors expressing mutant HTT in the striatum. We are currently developing three cell-type specific mice models of HD, expressing mHTT in neurons or astrocytes or both in mouse striatum. In the neuron-specific model we already characterized several pathological hallmarks of HD and motor deficits.

The aim of this project is to precisely analyze the specific contribution of neurons and astrocytes with a multilevel approach. In these cell-type specific models we will characterized the evolution of pathological markers, behavioral, metabolic and transcriptional dysfunctions. This project will bring important results for the understanding of fundamental aspects of Huntington’s disease and could be developed in the future for the evaluation of biomarkers or therapeutic approaches.