Patients with Alzheimer’s disease and other forms of dementia commonly experience sundown syndrome: a sudden worsening of confusion, agitation and aggression at the end of the day.
This daily pattern suggested that sundowning, as the phenomenon is also known, may be governed by the body’s internal biological clock. Synchronized by light and darkness, the circadian clock exerts control over wake/sleep cycles, body temperature, digestion, hormonal cycles and other physiological and behavior patterns. Whether the circadian clock regulated aggressive behavior was unknown
Now, for the first time, Harvard Medical School neuroscientists at Beth Israel Deaconess Medical Center have demonstrated circadian control of aggression in male mice and have identified the specific neurons and circuitry regulating the daily pattern. The insight opens the door to potential opportunities for managing the evening-time agitation common in patients with degenerative neurological disorders. The study was published in Nature Neuroscience.
“Sundowning is often the reason that patients have to be institutionalized, and if clinicians can control this circuit to minimize aggressiveness at the end of the day, patients may be able to live at home longer,” said senior author Clifford Saper, the HMS James Jackson Putnam Professor of Neurology and chair of the department of neurology at Beth Israel Deaconess.
“We examined the biological clock’s brain circuitry and found a connection to a population of neurons known to cause violent attacks when stimulated in male mice. We wanted to know if this represented a propensity for violence at certain times of day,” he said.
Saper and colleagues observed aggressive interactions between male mice. They observed the resident mice defending territory against intruders introduced to residents’ cages at different times throughout the day. Counting the intensity and frequency of residents’ attacks on intruders revealed for the first time that aggression in male mice exhibits a daily rhythm.