Analysis of Nonmotor Features in Murine Models of Huntington Disease

Huntington disease (HD) has traditionally been considered mainly a movement disorder with basal ganglia neurodegeneration. Nevertheless, nonmotor aspects are part of the clinical manifestation and have recently gained increasing attention. These features include psychiatric, cognitive, and metabolic disturbances and often precede the onset of motor dysfunction by many years. The interest to establish causative links between HD pathology and behavior and the need to develop effective therapies have motivated the research field to investigate to what extent murine HD models present nonmotor disturbances. As a result, there are now a number of well-established mouse models that successfully mirror several HD nonmotor features, such as anxiety, depression, cognitive impairment, and metabolic dysfunction. This chapter reviews the most widely used murine models for the study of nonmotor phenotypes in HD and the different tests used to assess these features and describes the main results demonstrating nonmotor disturbances in HD mouse models.