A Good Night's Sleep?

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Science  28 Jan 2005:
Vol. 307, Issue 5709, pp. 483
DOI: 10.1126/science.307.5709.483d

One of the distressing symptoms of progressive neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's diseases is the severe disruption of sleep patterns, which leads to anxiety and distress in both patients and their caregivers. Two recent papers now shed light on the cellular and molecular mechanisms of sleep disruption in Huntington's disease (HD).

Petersen et al. find that HD patients and R6/2 mice (which mimic many of the features of human HD) exhibit progressive loss of brain neurons in the hypothalamus— a key regulator of many different processes, including sleep. The hypothalamic neurons that die in HD patients and mice produce the neuropeptide orexin, loss of which has been implicated in narcolepsy. Decreasing amounts of orexin in the cerebrospinal fluid of HD patients could thus be used as a marker of HD progression.

Orexin neurons in the hypothalamus also innervate the suprachiasmatic nucleus, which drives circadian sleep/wake cycles by regulating the transcription of several key “clock” genes. Morton et al. report that progressive dis-ruption of circadian behavior in R6/2 mice is accompanied by marked alterations in the expression of the mPer2 and mBmal1 clock genes. These findings help to explain why HD patients suffer from markedly increased daytime sleepiness and night wakefulness, and hopefully will contribute to better management of these distressing symptoms. — OMS

Hum. Mol. Genet. 14, 39 (2005); J. Neurosci. 25, 157 (2005).

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