Circadian Rhythms: What Makes Us Tick

By: Simerjeet Mudhar


Image Credit: Flickr @ National Human Genome Research Institute

Every organism has a system that regulates certain functions in the body over a fixed time period. This system is called the circadian rhythm, which is defined as the set of behavioral, physical, and mental changes that follow a cycle with a period lasting approximately 24 hours in response to the environment. The term “circadian rhythms” refer to a number of biological cycles, such as those of hormones and body temperature. However, circadian rhythms are most commonly used to describe sleep cycles in humans. Oftentimes, when one has not gotten a lot of sleep, there is a noticeable shift in the periods when one is alert and drowsy. This can lead to detrimental effects on the well-being of individuals, especially as when one cycle is disrupted, other cycles can be unregulated as well.

Although a circadian rhythm is a regulation of bodily processes over a time period, it should not be confused with biological clocks. Biological clocks are different from circadian rhythms in that the phrase “biological clocks” is an umbrella term which encompasses circadian rhythms. Aside from circadian rhythms, there are two other types of biological clocks: ultradian and infradian rhythms. At times, the circadian rhythm can be described as a diurnal rhythm as well, especially when the sleep cycle is involved. However, the circadian rhythm maintains its separate identity as a 24 hour clock which reacts to external stimuli.

The circadian rhythm is primarily controlled by the suprachiasmatic nucleus (SCN) region in the hypothalamus of the brain. This area of the brain is able to receive direct input from the eyes, which is how it receives external stimuli to act upon. Ultimately, the SCN functions as a sort of master clock that translates environmental stimuli into instructions for the body. Studies have shown that there is a singular peptide necessary for regular circadian rhythm functions called Neuromedin S, which serves as a cellular pacemaker. This peptide is secreted by a cluster of SCN neurons, and in turn activates the neurons around it and induces phase shifts for neurons associated with locomotor activity (brain function and movement). Research done on mice has shown that when the timings of Neuromedin S release are staggered or manipulated, it alters the circadian rhythm of the entire animal, leading to differences in sleep/wake times, hunger periods, as well as behavioral changes.


Image Credt: Flickr @ Robert Sullivan

The circadian rhythm itself is managed by 2 proteins, CLOCK and BMAL1. In the brain, these two proteins heterodimerize (merge) and induce the transcription of particular genes. These genes are eventually translated into proteins called Per1 and Cry1. These two proteins manage a variety of functions, from light-dependant reactions to regulating certain aspects of the immune system. However, the secretion of Per1 and Cry1 inhibit CLOCK and BMAL1 from transcribing more genes to produce more Per1 and Cry1. Eventually, concentrations of Per1 and Cry1 fall too low and so without the proteins to inhibit their function, CLOCK and BMAL1 continue to transcribe the genes to make more Per1 and Cry1 to regulate certain aspects of the body. In this way, the inhibition of CLOCK and BMAL1 form a cycle. This cycle regulates the timings of when Per1 and Cry1 are functional, which results in a clock-like mechanism. Although more in depth research remains to be done about the specificities of the mechanisms of CLOCK and BMAL1, it can be said that these proteins are an integral part of the circadian rhythm regulating mechanism.


The circadian rhythm is necessary for regulating bodily processes; however, it is possible for the system to be disrupted. When the rhythm has been disrupted, it means that the clock function shifted a little, similar to how an alarm clock may read the wrong time. The most common disruption in the rhythm is with the sleep/wake cycle. In this day and age, when it gets dark outside, a common response is to turn on the lights. However, these bright lights cause the brain to send a signal to cut off melatonin supply. This is because these bright lights are interpreted by the brain as sunlight. The brain has learned that one should be awake and moving during the day when there is a lot of sunlight, and so reduces the supply of melatonin, a substance which helps someone fall asleep. In this way, bright lights before going to bed can make it hard for someone to fall asleep, and so the circadian rhythms are off balance. Additionally, melatonin has the ability to protect the DNA from excessive damage. If melatonin is constantly suppressed because of the presence of bright lights, then it is possible that DNA can sustain extensive damage, resulting in cancer.


Cancer is an extreme result of the disruption of circadian rhythms. Normally when rhythms are not synced, it can lead to problems involving sleep disorders, metabolic issues, psychiatric disorders, weight gain, and slower thinking. Some studies have also connected the malfunctioning of the circadian rhythm to Alzheimers. When the circadian rhythm is not working properly, mice have been shown to undergo behavioral and physical changes, become more impulsive, and exhibit changes in the medial prefrontal cortex, which is the part of the brain that controls executive function. It should be noted that minor cases of circadian rhythm disruption can be fixed. For example, for sleep troubles, one can dim the lights a bit before bed in order to prevent the brain from cutting off melatonin supply, which can help someone sleep. In this way, the circadian rhythm is the fundamental system which manages and regulates life’s daily functions.


Citations:

https://www.sleepfoundation.org/articles/what-circadian-rhythm

https://www.sciencedaily.com/releases/2009/10/091026225744.htm

https://www.sciencedaily.com/releases/2015/03/150317195954.htm

https://www.nigms.nih.gov/education/fact-sheets/Pages/circadian-rhythms.aspx

https://www.healthline.com/health/biological-rhythms

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762864/

https://www.ncbi.nlm.nih.gov/pubmed/18751931

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647832/

https://www.embopress.org/doi/full/10.1038/sj.emboj.7600526

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811223/


What did you learn?

Questions


1. What is the main peptide responsible for regulating circadian rhythms?


Neuromedin S is responsible for the regulation of circadian rhythms, as it serves as a cellular pacemaker. It is secreted by SCN neurons, and in turn activates the neurons around it and induces phase shifts for neurons associated with brain function and movement.


2. How is the dysfunction of circadian rhythms related to cancer?


In the sleep/wake cycle, bright lights cause the brain to stop the supply of melatonin, which makes you sleepy. These bright lights trick the brain into thinking there is sunlight, and so the brain cuts off the melatonin supply because people are usually awake during the day. However, melatonin protects against extensive DNA damage, and when the supply is consistently cut off by all the bright lights someone may be surrounded by, it is possible that DNA will undergo damage. Cancer is when cells with extensive DNA mutations continue to divide at a rapid pace. Because melatonin is not protecting the DNA from mutation, the DNA could continue to mutate and the end result would be cancerous cells.


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