Prevention of appearance of severe Huntington's disease symptoms in the R6/1 mouse model by early administration of 4′,5,7-trihydroxyisoflavone

Background Recent reports indicated that 4′,5,7-trihydroxyisoflavone (genistein) can improve biochemical disorders and correct behavioral disturbances in cellular and animal models of Huntington's disease (HD), acting thorough stimulation of autophagy-dependent degradation of mutant huntingtin aggregates. Effects in the mouse HD model was tested previously only after appearance of symptoms of HD. Objective The aim of this work was to assess the efficacy of genistein in preventing the appearance of symptoms in the R6/1 mouse model of HD, using both males and females. Methods A battery of behavioral tests (Rota-rod, elevated-plus maze, Morris water maze, monitoring of movements in actometer) was used, and selected biochemical and hematological parameters were determined in control (wild-type) and R6/1 (HD) mice (males and females) treated with either orally-administered genistein at 150 mg/kg/day or water (control). The treatment was initiated at 7 th week of life (while the first symptoms appear at 14–16 week in this HD model), and was continued until 30 th week. Results Administration of genistein resulted in extension of life span and prevention of appearance of HD symptoms in R6/1 mice. The immunological and biochemical parameters were comparable between wild-type and R6/1 mice treated with genistein, whereas the untreated HD animals revealed significant differences relative to controls. Conclusions Genistein appeared to be effective in preventing the appearance of severe symptoms of HD in the mouse R6/1 model, indicating that this compound might be considered as a potential anti-HD drug.