Abstract
BackgroundThe R6/1 mouse line is one of the most widely employed models of Huntington Disease (HD), a complex syndrome characterized by motor and non-motor deficits. Surprisingly, its behavioral phenotype during the early phases of the pathology when the motor impairments are not manifest yet has been poorly investigated. It is also not clear whether the expression of HD-like symptoms at the pre-motor stage in this mouse model differs between the two sexes.MethodsMale and female 12 weeks-old R6/1 mice and their wild-type littermates were tested on a battery of tests modeling some of the major neuropsychiatric non-motor symptoms of HD: alterations in social interest, social interaction and communication, as well as disturbances in prepulse inhibition of the acoustic startle response (PPI) and circadian patterns of activity. The lack of motor symptoms was confirmed during the entire experimental period by means of the tail test for clasping.ResultsR6/1 mice displayed marked alterations in all social behaviors which were mainly observed in males. Male R6/1 animals were also the only ones showing reduced body weight. Both male and female transgenic mice displayed mild alterations in the circadian activity patterns, but no deficits in PPI.ConclusionsThese results demonstrate the validity of the R6/1 mouse in mimicking selected neuropsychiatric symptoms of HD, the social deficits being the clearest markers of the pre-motor phase of the pathology. Furthermore, our data suggest that male R6/1 mice are more suitable for future studies on the early stages of HD.
Highlights
Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene resulting in a mutated polyglutamine tract in the huntingtin protein [1]
Huntington Disease (HD) is observed in individuals with more than 39 CAG repeats, and it develops through a triad of complex symptoms
The present study investigated the expression of HD-like neuropsychiatric symptoms at the pre-motor stage of the pathology in R6/1 mice of both sexes
Summary
Huntington’s disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene resulting in a mutated polyglutamine tract in the huntingtin protein [1]. They are followed by cognitive decline and precede motor impairments by several years [2,3,4,5,6,13]. Its behavioral phenotype during the early phases of the pathology when the motor impairments are not manifest yet has been poorly investigated It is not clear whether the expression of HD-like symptoms at the pre-motor stage in this mouse model differs between the two sexes
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