The absence of the aryl hydrocarbon receptor in the R6/1 transgenic mouse model of Huntington?s disease improves the neurological phenotype

Huntington?s disease (HD) is an inherited neurodegenerative disorder caused by an abnormal CAG repeat expansion in the huntingtin gene coding for a protein with an elongated polyglutamine sequence. HD patients present choreiform movements, which are caused by the loss of neurons in the striatum and cerebral cortex. Previous reports indicate that the absence of the aryl hydrocarbon receptor (AhR) protects mice from excitotoxic insults and increases the transcription of neurotrophic factors. Based on these data, we evaluated the effects of the lack of the AhR on a mice model of HD, generating a double transgenic mouse, expressing human mutated huntingtin (R6/1 mice) and knockout for the AhR. Our results show that the body weight of 30-week-old double transgenic mice is similar to that of R6/1 mice; however, feet clasping, an indicative of neuronal damage in the R6/1 animals, was not observed. In addition, motor coordination and ambulatory behavior in double transgenic mice did not deteriorate over time as occur in the R6/1 mice. Moreover, the anxiety behavior of double transgenic mice was similar to wild type mice. Interestingly, astrogliosis is also reduced in the double transgenic mice. The present data demonstrate that the complete loss of the AhR reduces the motor and behavioral deterioration observed in R6/1 mice, suggesting that the pharmacological modulation of the AhR could be a therapeutic target in HD.

Automated summary

The lack of AhR reduces neurological damage and behavioral deterioration in a mouse model of Huntington's disease, suggesting that pharmacological modulation of AhR could be a potential therapeutic target for HD.