Circadian dysfunction in huntington’s disease

Abstract

Sleep disorders are common in Huntington’s disease (HD) patients and develop early in the disease process. Among a number of possible mechanisms that underlie sleep disruption, there is evidence that circadian system dysfunction is a contributing factor. Using the BACHD mouse models of HD, we have determined that at the onset of symptoms, rhythmic spontaneous electrical activity of neurons within the suprachiasmatic nucleus (SCN) is disrupted even though the molecular clockwork is still functional. These findings suggest that reduced SCN output may underlie disrupted timing of sleep and have wide ranging impact throughout the body. The mechanism underlying this deficit is not yet known, but mitochondrial dysfunction and oxidative stress are likely involved. Our animal model findings raise the possibility that disordered sleep and circadian function experienced by HD patients may be an integral part of the disease, and we speculate that circadian dysfunction may accelerate the pathology underlying HD. If these hypotheses are correct, we should focus on treating circadian misalignment and sleep disruptions early in disease progression.