Scientists have zeroed in on a cluster of brain cells that controls the sleep and wake cycles in most mammals and may explain why people don’t feel jet-lagged when they run a fever.
According to the study by researchers at the Johns Hopkins University School of Medicine, a clump of just a few thousand brain cells known as the suprachiasmatic nucleus (SCN) about the size of a mustard seed, controls the ebb and flow of the majority of bodily processes in mammals including sleep and wake cycles.
The researchers used direct evidence in mice in determining how the cell clusters control sleep and relay light cues about night and day throughout the body.
In previous experiments the research team was able to disrupt the normal function of the SCN without physically removing it and damaging the optic nerve. They then attempted to identify genes involved in the development of the mouse hypothalamus, pinpointing the LHX1 gene, which seemed to be the earliest to “turn on” in the development of the fetal SCN.
In the most recent experiment, the research team used a customized genetic tool to delete the LHX1 just from cells that make up the SCN in the mice, which showed experiences of severely disrupted circadian rhythms, while they could still be weakly synchronized to light cycles.
By doing this, the cells no longer produced six small signaling proteins known to coordinate and reinforce their efforts, a biochemical process known as coupling.
The sleep times of the mice became random, whether they were kept in constant light, constant darkness or normal cycles of both. The scientists also noticed that the core body temperature of the mice did not cycle normally.
Seth Blackshaw, Ph.D., professor of neuroscience at the Johns Hopkins University School of Medicine, explained that the core temperature in both mice and humans generally aren’t disturbed by large temperature changes.
Normal SCN cells in the lab keep cycling in synchrony without regard to temperature pulse but previous research from a separate group proved that they could be reset by temperature changes if they could no longer signal to each other.
Blackshaw and his team then injected the mice—kept in the dark—with a molecule found in bacterial cell walls, which makes them run a fever in response to the perceived threat and sent their core temperatures to resume regular cycling.
“These results suggest that the SCN is indeed responsible for the temperature resistance of circadian rhythms in live animals, and it shows us how important SCN coupling is,” Blackshaw said. “It also bolsters the idea that the body’s other physiologic cycles, such as hunger and hormone secretion, are synchronized by the SCN through its regulation of core body temperature.”
According to Blackshaw, scientists have been well aware that SCN functions as a “master clock” to synchronize sleep and other circadian rhythms in humans and other mammals but its importance in regulating sleep was up for debate.
“If you surgically removed the SCN in mice, their sleeping and waking were no longer immediately influenced by light but you can’t remove the SCN without also severing the optic nerve that brings light information to it from the retina,” he said. “So no one knew if this resistance to light was due to the missing SCN or the missing optic nerve.”
The latest breakthrough may enable drug developers to have a better idea which component to target and how. For example, to treat jet lag developers may be able to briefly block LHX1 so that the SCN cells uncouple and become easier to reset, either by light or temperature.
The study was published in Current Biology.
Other authors of the report include Abhijith Bathini, Jonathan Ling, Benjamin Bell, Mark Wu, Philip Wong and Samer Hattar of the Johns Hopkins University School of Medicine; Tara LeGates of the Johns Hopkins University; Ethan Buhr and Russell Van Gelder of the University of Washington, Seattle; and Valerie Mongrain of the University of Montreal.