CHICAGO, April 3 (Xinhua) -- Disrupted sleep-wake cycles might protect the brain, a study of the Northwestern University (NU) shows.
In the study, NU researchers employed the fruit fly model of Huntington's disease, a well-studied model organism for both circadian rhythms and neurodegenerative diseases.
Although fruit flies might seem completely different from humans, the neurons that govern flies' sleep-wake cycles are strikingly similar to humans'. Fruit flies that have the mutant Huntington's gene also demonstrate similar symptoms as humans with the disease: reduced lifespan, motor deficits, neurodegeneration, disrupted circadian rhythms and an accumulation of diseased proteins in the brain, which aggregate and cause neurons to die.
The researchers altered the flies' circadian rhythms in two different ways. For one group of flies, they altered the flies' environment by changing the daily timing of light-dark cycles. This manipulation caused the flies to live a 20-hour day instead of a 24-hour day. And for another group of flies, the researchers mutated a gene that is well known for controlling the internal circadian clock.
In both cases, the mutant Huntington's disease proteins aggregated less and fewer neurons died.
The researchers were so fascinated by the result that they decided to screen through dozens of clock-controlled genes to pinpoint one that also might similarly protect the brain against neurodegenerative diseases.
They zeroed in on a gene that encodes the "heat shock organizing protein," or "hop" for short. Not only is hop controlled by the body's circadian clock, the gene is also responsible for protein folding.
As misfolded proteins can result in many different neurodegenerative diseases, the researchers knocked down the hop gene in flies with the protein that causes Huntington's disease, and were surprised to find that knocking down the gene restored the flies' arrhythmic circadian clocks, reduced the aggregation of diseased proteins in the brain and reduced the number of neurons killed by those proteins.
"We thought that inhibiting this gene that helps your proteins fold properly would make things worse, but they got better," said Ravi Allada, an NU circadian rhythms expert who led the research. "It again shows that a little bit of stress is probably good."
In the next step, the researchers plan to test this method in a fruit fly model of Alzheimer's disease. They believe that targeting and knocking down the hop gene could potentially be an early intervention for slowing the progression of various neurodegenerative diseases.
The study was published Tuesday in the journal Cell Reports.
