A team of American scientists has demonstrated the internal biological clocks may regulate the aggressive behaviors of male mice, opening the door to potential opportunities for managing the evening-time agitation common in patients with degenerative neurological disorders.
In a study published on Monday in the journal Nature Neuroscience, the researchers observed aggressive interactions between male mice -- 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, said the paper's senior author Clifford B. Saper at Beth Israel Deaconess Medical Center, a Boston-based research institute under Harvard University.
"The mice were more likely to be aggressive in the early evening around lights out, and least aggressive in the early morning, around lights on," Saper said. "It looks like aggressiveness builds up in mice during the lights on period, and reaches a peak around the end of the light period."
Then, the scientists used genetics-based tools to manipulate neurons known to regulate the central circadian clock.
When Saper's team inhibited these neurons by disabling their ability to produce a specific neurotransmitter, the mice lost the daily waxing and waning of their aggressive tendencies.
These genetically manipulated mice were more aggressive overall, demonstrating a significant increase in total time attacking intruders.
Using optogenetics, a technique that uses light to activate or deactivate targeted brain cells, to map brain circuitry revealed two parallel pathways between the biological clock and a population of neurons in a sub-region of the hypothalamus known to cause violent attacks when stimulated in male mice.
Researchers said patients with Alzheimer's disease and other forms of dementia commonly experience the sundown syndrome, a sudden worsening of confusion, agitation and aggression at the end of the day.
"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 Saper.
"Our results in mice mimic the patterns of increased aggression seen in patients during sundowning," said Saper.
"This new research suggests this pathway may be compromised in neurodegenerative diseases. Examining changes to this pathway in patients could provide insight into future interventions that could greatly improve the quality of life for patients and caregivers alike."
