Sex-dependent changes in social behaviors in motor pre-symptomatic R6/1 mice
PLoS ONE. 2011-05-16; 6(5): e19965
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Pietropaolo S(1), Delage P, Cayzac S, Crusio WE, Cho YH.
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Université
de Bordeaux and CNRS UMR 5287, Talence, France.
BACKGROUND: The 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.
METHODS: Male 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.
RESULTS: R6/1 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.
CONCLUSIONS: These 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.