Sleep Problems Tied to Neurodegenerative Conditions

Brain cell damage similar to that seen in Alzheimer disease and other disorders results when a gene that controls the sleep-wake cycle and other bodily rhythms is disabled, according to researchers at the Washington University School of Medicine in St Louis and the University of Pennsylvania in Philadelphia.

Sleep loss increases the risk of Alzheimer disease, and disrupted sleeping patterns are among the first signs of the disorder, it was noted.

The researchers found evidence to indicate that disabling a circadian clock gene that controls the daily rhythms of many bodily processes blocks a part of the brain’s housekeeping cycle that neutralizes free radicals.

Musiek and coauthors studied mice that lacked Bmal1, a master clock gene. Activities that normally occur at particular times of the day are disrupted when the gene is not present.

The researchers found that as the mice aged, many of their brain cells became damaged and did not function normally. The patterns of damage were similar to those seen in Alzheimer disease and other neurodegenerative disorders. The brain cell injury in the mice far exceeded that normally seen in aging mice.

The researchers examined the production of key antioxidant enzymes, which usually neutralize and help clear free radicals from the brain, thereby limiting damage. They found that levels of several antioxidant proteins peak in the middle of the day in healthy mice but that the surge is absent in mice that lack Bmal1. They are trying to identify more specifics about how problems in clock genes contribute to neurodegeneration, with and without influencing sleep.

Impaired clock gene expression in mice can cause a variety of pathologies, including diabetes mellitus, vascular disease, obesity, and accelerated aging, the authors noted.

They suggested that further study of the regulation of circadian clock genes in non–suprachiasmatic nucleus brain regions in aging and neurodegenerative diseases is warranted and that therapies targeted at bolstering positive-limb clock gene expression in the brain might have neuroprotective effects.

The study was published on November 25, 2013, in The Journal of Clinical Investigation.