UCLA

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a CAG repeat expansion in the huntingtin gene. Patients report cognitive and psychiatric difficulties as well as disruptions in their sleep/wake cycles prior to the onset of the motor symptoms. I assessed three HD mouse models (transgenic BACHD, Q175 knock-in, and 3-NP mitochondrial toxin treatment) and show that each model exhibited sleep and circadian deficits. Next, I sought to stabilize and rescue the circadian rhythms of the BACHD mouse model by keeping the mice on a regular feeding schedule. Measurements of cognition, motor coordination, sleep and circadian rhythms were taken before and after a 3-month treatment. My results indicate that scheduled feeding can improve circadian, sleep, and cognitive performance. While motor performance did not improve, the tests showed no further decline during treatment. Thus, the experimental data supports the use of temporally restricting feeding as a lifestyle-based therapeutic.