Anxiety, memory, and social impairments in the YAC128 mouse model of Huntington's disease.

Abstract

Background: Huntington's disease (HD) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the huntingtin protein. HD is characterized by a progressive decline in motor functions. This decline includes involuntary movements (chorea) and the worsening of controlled motions caused mainly by neuronal dysfunction in the striatum. In addition to the deterioration of motor symptoms, HD patients also suffer from cognitive changes, mood swings, apathy, depression, outbursts of anger, psychosis, and social withdrawal.

Objective: A comprehensive examination of cognitive, affective, and social changes in the HD mouse model is required for the development of combined therapy for both motor and non-motor deficits in HD.

Methods: The behavioral tests for anxiety, memory, and social traits were used in this study.

Results: YAC128 HD transgenic mice exhibited anxiolytic behavior in the novel brightly illuminated environment of the open field and light-dark place preference tests. Moreover, YAC128 HD mice also suffered from a decline in their recognition memory during the novel object recognition test. YAC128 HD mice demonstrated reduced exploration interest during the open field with a non-social target as well as during the first day of the three-chamber social test. Social interaction was also impaired in YAC128 HD mice as it was shown in the social interaction with resident intruder test.

Conclusions: YAC128 HD mouse model may be used as a model system to test the possible treatments for both motor and non-motor symptoms including memory loss, agitation and social withdrawal.