Confocal microscopy image of neuronal cells (nuclei in blue) of the suprachiasmatic nuclei after exposure to light early during the night, showing calcium channels (red) and Calmodulin (yellow) that translocated to the membrane around the nucleus in response to light. Image credit: Brenna et al. (CC BY 4.0)
Our bodies evolved to follow daily rhythms, influencing our sleeping and waking patterns and our usual mealtimes. These rhythms are based on circadian clocks that allow our bodies to stay in tune with the day-night cycle in our environment.
Circadian rhythms are controlled by a set of biological mechanisms termed molecular clocks, which are found in every cell and organ. The body also has a ‘master clock’, which is in a part of the brain called the suprachiasmatic nuclei (SCN). The SCN is the body’s main ‘timekeeper’ and coordinates all our daily cycles of biological processes and behaviours.
Molecular clocks also respond to artificial stimuli, which can cause shifts in circadian rhythms. These alterations disrupt the normal alignment of our bodily processes with the environmental day-night cycle, meaning that our bodies work less efficiently. For example, light exposure early during the night changes our circadian rhythms so that we go to sleep and wake up later, a phenomenon called phase delay.
The enzyme CDK5 is part of the SCN’s master clock. CDK5 helps control normal circadian rhythms: it is more active in the dark (i.e., at night), when it helps to turn off genes that respond to light, and is inactive in light conditions, ensuring that the light response genes stay switched on during the day. Since CDK5 is also involved in many neurological diseases linked to disturbed circadian rhythms, Brenna et al. wanted to determine whether it also controlled the circadian shift caused by light exposure early during the night.
To simulate this mistimed light, mice were exposed to 15 minutes of bright light two hours after the onset of darkness in the laboratory light/dark cycle. Biochemical and genetic analysis revealed that in standard mice, this reduced CDK5 activity in the SCN, switched light response genes back on, and resulted in phase delay. However, light exposure did not cause any shift in behaviour in genetically engineered mice lacking CDK5, confirming that CDK5 was indeed responsible for the phase delay observed.
These results contribute to our understanding of the mechanisms behind the body’s response to stimuli that force our internal clock out of sync with our environment. Brenna et al. hope that targeting CDK5 may one day help us cope better with circadian misalignment and the health problems associated with it, especially for people affected by jet lag or shift work.
