Broken Cellular Clock Linked to Brain Damage Associated with Alzheimer's

Scientists may have uncovered the reason behind the strong connections between sleep problems and neurodegenerative conditions such as Alzheimer's disease. It turns out that brain cell damage similar to that seen in Alzheimer's disease and other disorders results when a circadian clock gene that controls the sleep-wake cycle and other bodily rhythms is disabled.

This circadian clock gene actually controls the daily rhythm of many bodily processes. Yet by disabling this gene, the researchers managed to block a part of the brain's housekeeping cycle that neutralizes dangerous chemicals known as free radicals.

"Normally in the hours leading up to midday, the brain increases its production of certain antioxidant enzymes, which help clean up free radicals," said Erick Musiek, one of the researchers, in a news release. "When clock genes are disabled, though, this surge no longer occurs, and the free radicals may linger in the brain and cause more damage."

In order to better study this gene, the researchers looked at mice. More specifically, they examined rodents lacking a master clock gene called Bmal1. Without this gene, activities that normally occur at particular times of the day were disrupted. For example, the mice slept equally in the day and night with no circadian rhythm without this gene.

So what other effects did the mice suffer? As the mice aged, many of their brain cells became damaged and did not function normally. In fact, the patterns of damage were similar to those seen in Alzheimer's disease and other neurodegenerative disorders.

"Brain cell injury in these mice far exceeded that normally seen in aging mice," said Musiek in a news release. "Many of the injuries appear to be caused by free radicals, which are byproducts of metabolism. If free radicals come into contact with brain cells or other tissue, they can cause damaging chemical reactions."

These findings reveal a little bit more about how Bmal1 could play a crucial role in the health of an individual. More specifically, it shows a bit more about how problems in clock genes could contribute to neurodegeneration. This, in turn, could inform future studies on Alzheimer's disease and other conditions that impact individuals.

The findings are published in the Journal of Clinical Investigation.