Abstract
Background: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by CAG repeat expansions in the HTT gene. Somatic repeat expansion in the R6/1 mouse model of HD depends on mismatch repair and is worsened by base excision repair initiated by the 7,8-dihydroxy-8-oxoguanine-DNA glycosylase (Ogg1) or Nei-like 1 (Neil1). Ogg1 and Neil1 repairs common oxidative lesions.Methods: We investigated whether anthocyanin antioxidants added daily to the drinking water could affect CAG repeat instability in several organs and behaviour in R6/1 HD mice. In addition, anthocyanin-treated and untreated R6/1 HD mice at 22 weeks of age were tested in the open field test and on the rotarod.Results: Anthocyanin-treated R6/1 HD mice showed reduced instability index in the ears and in the cortex compared to untreated R6/1 mice, and no difference in liver and kidney. There were no significant differences in any of the parameters tested in the behavioural tests among anthocyanin-treated and untreated R6/1 HD mice.Conclusions: Our results indicate that continuous anthocyanin-treatment may have modest effects on CAG repeat instability in the ears and the cortex of R6/1 mice. More studies are required to investigate if anthocyanin-treatment could affect behaviour earlier in the disease course.
Highlights
Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG expansion in exon 1 of theHuntingtin (HTT) gene encoding the polyglutamine protein HTT 1
Stoichiometries of base excision repair (BER) proteins correlates with the degree of somatic instability seen in the striatum and cerebellum of HD transgenic mice 7
Age-dependent CAG repeat expansion are reduced in R6/1 mice lacking the BER enzyme 7,8-dihydroxy-8-oxoguanine (8-oxoG)-DNA glycosylase (Ogg1)8
Summary
Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG expansion in exon 1 of theHuntingtin (HTT) gene encoding the polyglutamine protein HTT 1. Stoichiometries of base excision repair (BER) proteins correlates with the degree of somatic instability seen in the striatum and cerebellum of HD transgenic mice 7. Age-dependent CAG repeat expansion are reduced in R6/1 mice lacking the BER enzyme 7,8-dihydroxy-8-oxoguanine (8-oxoG)-DNA glycosylase (Ogg1). The BER DNA glycosylase Nei-like 1 (Neil1) has recently been shown to be a genetic modifier of both somatic and germline CAG repeat instability in R6/1 mice 9. Deletion of the mismatch repair proteins Msh and Msh has been shown to abolish somatic expansion in several HD mouse models [10,11,12]. Somatic repeat expansion in the R6/1 mouse model of HD depends on mismatch repair and is worsened by base excision repair initiated by the 7,8-dihydroxy-8-oxoguanine-DNA glycosylase (Ogg1) or Nei-like 1 (Neil).
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