AUG 10, 2015

Mellow or Mean?

WRITTEN BY: Ilene Schneider
Losing sleep means physiological effects and behavioral changes, and people have studied the link between sleep loss and aggression. "Sleep is essential for the renewal and restoration of the body. If you don't get enough, it can result in irritability, impatience, inability to concentrate, weight gain, and increased stress hormone levels, and it alters the body's ability to ward off disease and illness," wrote Sarah Pedersen and Langan Denhard in a National Center for Health Research Study (http://center4research.org/child-teen-health/sleepiness-aggressive-behavior-and-bullying/).

Much of that is logical. Still, not everybody completely agrees with that conclusion.

Because it is hard to distinguish sleep loss effects from stress responses in rodent and human models, a team of researchers from the Perelman School of Medicine at the University of Pennsylvania used fruitflies to understand the cellular and molecular mechanisms of aggression and sleep. In an article published in eLife, they described how sleep deprivation reduces aggression in fruitflies and affects their reproductive fitness and identified a related molecular pathway that might govern recovery of normal aggressive behaviors (http://www.uphs.upenn.edu/news/News_Releases/2015/07/sehgal/).

Lead author Matthew Kayser, M.D., Ph.D., an assistant professor of psychiatry, and his looked at several chemicals that have been associated with aggression in fruitflies and other species. As he explained, "There has been a lot of work on these monoamines, the same ones that are potentially involved in some aspects of mammalian aggression. We asked what happens if we try to activate dopamine receptors or octopamine [the insect version of norepinephrine in mammals], a type of monoamine, after sleep loss in flies."

When the flies received the chlordimeform (CDM), an octopamine agonist and the dopamine agonist L-DOPA and were sleep deprived, the researchers found that CDM rescued aggressive behavior, but L-DOPA did not. According to Kayser, "If you activate octopamine receptors, you rescue the fighting behavior. "The other drug L-DOPA makes them really active, but they're not fighting." Neither drug affected fighting behaviors when flies were not sleep deprived, but then they went from fighting a great deal to sharing resources and not fighting very much.

The team also studied the effects of reduced aggression on social behavior, specifically reproductive behavior and success. They found that sleep deprivation affected sexual fitness. The molecule CDM rescued aggression and mating fitness in the sleep-deprived flies, while L-DOPA had no effect.

Now the researchers want to figure out the neurobiological mechanisms that control the sleep-aggression link. As Kayser said, "Our work suggests that somehow downstream of the sleep neuron pathway, there's a connection with aggression neurons, so we really want to understand what those are."

Because cellular and molecular mechanisms involved in behaviors such as sleep and aggression are highly conserved across species, the researchers think there is a possibility of translating the present research to humans. "I definitely see the potential for translation here, although it may be in the distant future," said senior author Amita Sehgal, Ph.D, a professor of neuroscience, director of the Chronobiology Program and a Howard Hughes Medical Institute (HHMI) investigator.