B009 Evolution of the psychiatric phenotype in the early stages of a Huntington’s disease preclinical model

<h3></h3> Huntington’s Disease (HD) is a monogenic and neurodegenerative disorder caused by an abnormal amount of CAG repeats in the exon 1 of the huntingtin gene, responsible for numerous transcriptional and cellular process dysfunctions, leading to neuronal death. HD mainly targets the medium spiny neurons of the striatum and more broadly the corticostriatal pathway, but other brain areas, such as the hippocampus, are also affected at more advanced stages of the disease. These deregulations are responsible for a triad of symptoms, consisting in cognitive and psychiatric symptoms that occur prior to the emergence of motor disturbances. In this ongoing preclinical study, we focus specifically on the psychiatric side of HD which have not been explored in depth since most of the studies have focused on motor behavior alterations. We use the zQ175 mouse line, a transgenic knock-in mouse model expressing a truncated version of the human huntingtin gene that contains the mutant form of the huntingtin gene. Our goal is to thoroughly characterize the evolution of anxious- and depressive-like behaviors using a battery of specific behavioral tests (Open Field, Dark-Light, Elevated O-Maze, Nest Building, Splash, Three-Chamber and Forced Swimming tests) in heterozygous zQ175 mice at ages ranging from three to seven months. Therefore, our aim is to pinpoint a specific presymptomatic age at which heterozygous zQ175 mice show psychiatric-like phenotype, but not motor disturbances compared to their WT littermates. This study will provide informative data to further explore the cellular and molecular alterations involved in the psychiatric side of HD.