“It seems counterintuitive, but we showed that a little bit of stress is good,” Ravi Allada, a physician who heads the neurobiology department at the university’s Weinberg College of Arts and Sciences and Pathology, said in a statement. “We subtly manipulated the circadian clock, and that stress appears to be neuroprotective.”
The team says the findings could lead to new strategies for preventing or slowing the onset of progressive brain diseases such as Huntington’s disease, a fatal disorder that kills nerve cells and damages the brain. As with other progressive brain diseases, people who have Huntington often undergo profound changes to their sleep cycles, such as sleeping more than usual or having difficulty sleeping.
The study — which appeared Tuesday in the journal Cell Reports — focused on fruit flies, whose brains are wired for sleeping and waking cycles in ways that are similar to human brains. The team also used insects that had been genetically altered to mimic the progression of Huntington’s disease and show similar symptoms of the disorder, including shorter life span, mobility problems and disrupted circadian cycles.
To test the effect of disrupted sleep cycles, the team altered the usual 24-hour day rhythm for a group of insects. The fruit flies instead were put on 20-hour cycle whose periods of light and dark were altered every day — creating conditions not unlike having to hop a four-hour red-eye flight from Los Angeles to New York every day.
What the researchers found is that the relatively minor stress of daily jet lag seemed to strengthen the brain in important ways and slow the progression of Huntington’s disease: Fewer proteins linked to the disease were found, the team said, and fewer brain cells died.
The researchers then decided to see what would happen if they knocked out a gene that is controlled by circadian rhythms and plays a role in folding proteins — an especially inviting target, Allada said, because misfolded proteins have been shown to trigger some progressive brain diseases.
In this case, too, the fruit fly brains seemed to benefit, the researchers said. Allada said he plans further research into whether the same effect might be found in fruit flies that have been genetically modified to simulate Alzheimer’s disease.