In my last post, I wrote about the effect of blue light on the circadian rhythm (the body’s biological clock that sets the function for sleep and wake). It is amazing the role the circadian rhythm plays everyday in human and animal lives; clock genes control everything from organ function to eating cycles. But did you know that the circadian rhythm even affects whether or not you get up in the middle of the night to pee! And, did you know that your hair follicles can tell a lot about your sleep/wake habits? It’s true! Keep reading to find out what scientists have discovered.
In a recent study in Nature Communications, researchers looked at nocturnal enuresis (loss of urine during sleep in childhood) and nocturia (undesired waking at night to urinate, which afflicts 60-90% of people over 60 years). Nocturnal enuresis and nocturia are due to a mismatch between urine production in the kidneys and available storage in the bladder. Scientists compared mice genetically engineered to be without two circadian genes, Cryptochrome-1 andCryptochrome-2 (which results in a dysfunctional circadian rhythm), against normal mice. They discovered that the circadian gene called Rev-erbα controlled the production of Cx43, a protein that determines how much urine bladders hold. Though both the normal and genetically engineered mice put out the same volume of urine, the normal mice urinated more frequently when awake, compared with when they slept, while the genetically engineered mice urinated regardless of the time of day or night.
In the normal mice, researchers noted that Rev-erba produced more Cx43 during the day and decreased production at night. They concluded that even though the amount of urine produced didn’t change, the amount of Cx43 available determined how much room the bladder had to hold the amount of urine; more room at night and less room during the day. Researchers believe this disruption to the circadian rhythm is worth considering when studying nocturnal enuresis and nocturia, as it shows the disruption is not simply caused by a higher intake of fluids during the day.
A study in the April issue of Proceedings of the National Academy of Sciences looked at the effects of anesthesia post-surgery. An estimated “234 million operations requiring anesthesia occur around the world each year,” yet, the actions that occur to cause the sleep effect remain a mystery. The effects of anesthetics on the brain mimics some features of sleep and recent evidence indicates anesthetics are working, in part, on the same brain centers involved in the control of sleep, and that they may take over the sleep-controlling pathways in order to cause unconsciousness. Still, a patient awaking from general anesthesia wakes differently from a person awaking from a night’s sleep. Patients feel as though no time has passed and are disorientated.
For this study, researchers administered the anesthetics to honeybees. It is not new for researchers to use animals and insects to study how anesthetics work on humans. However, the honeybee is special in that its circadian rhythm determines at what time to forage for nectar and aids in navigation to and from the hive. Because of this, you can tell what time a honeybee thinks it is just by their behavior. No other mammal can do that.
The researchers used isoflurane, a common anesthetic used in surgeries, to drug the honeybees. After 6 hours of dosing, scientists tested the honeybees ability to navigate back to the hive. Because honeybees use both the position of the sun and their circadian rhythm for navigation, researchers expected the post-dosing honeybees they released in Germany and New Zealand to be off-course. And indeed they were roughly 90° off in the Southern Hemisphere and 62° off in the Northern Hemisphere. Researchers also noted an up to 3-hour delay in honeybees foraging for nectar post dosing.
Scientists also looked at the genetic effects of the anesthesia on the honeybees and found that mRNA (molecules carrying protein-building instructions) for two of the three clock genes was delayed between 4 and 5 hours after anesthesia. But, this only happened to honeybees dosed during the daytime, as honeybees dosed at night did not exhibit the same mRNA delay. This means, that isoflurane is time-dependent and the effect of the anesthetic on the circadian clock depends on the state of the clock when administered.
After waking from a few surgeries of my own, I can relate to this feeling of time lost. I feel you honeybee. And I thank you because, not only do you supply yummy honey, you helped demonstrate how the most commonly used anesthetic in the world causes a major shift of the circadian clock and that this effect can last for days post dosage. This information can alert the medical profession to monitor post-surgery patients who may be experiencing a form of “anesthesia-induced jet lag” which can have harmful consequences on patients physiology and metabolism. Armed with the knowledge of the effects on the circadian clock and treating those effects can certainly help post-surgery recovery.
And, finally (for this post. I guarantee more studies out there and coming up on circadian rhythm. I will very likely blog when I find them because they are fascinating!) I was a little more than surprised to find a 2010 study in the Proceedings of the National Academy of Sciences connecting hair and circadian rhythm. Yes. Hair.
In order to thoroughly understand the circadian rhythm, scientists must look at the circadian clock gene expression. Usually, this is done by examining white blood cells and oral secretions; at the time of the 2010 study, no simple method was available. But, a team of Japanese scientists decided to focus on the hair from scalps and beards, which contains cell-rich follicles that remain attached to the hairs even after plucking. Extracting RNA from the cells, they discovered that circadian gene activities peaked when subjects were awake, and early risers showed earlier peaking. Researchers then asked test subjects to disrupt their sleep-wake cycles by rising 4 hours later than normal and using bright light to mimic sunlight. After 3 weeks, the hair follicles circadian genes had also shifted by about 2.5 hours.
The scientists also looked at shift workers who alternated weeks working the 6 a.m. to 3 p.m. shift one week and the 3 p.m. to midnight shift the next week. The researchers found that circadian gene activity lagged 5 hours behind the workers’ lifestyles.
Examining hair follicles provided more reliable results than white blood cells (which experienced time delays during cell separation processing which can affect levels of expression of clock genes) and oral secretions (which were severely fragmented and so provided unreliable results that could not be repeated). The study of hair follicles is also a less invasive way to monitor patient’s circadian genes for medical problems they may be facing. And, it may offer more reliable results with less discomfort to the patient. Even better, the clock gene expression profiling data in this study revealed phenotypes from both internal and environmental factors. This even further aids in determining if the patient’s disorder is due to environmental factors (lifestyle) and/or endogenous factors (internal or genetic clock disfunctions).
Wow! Three major studies in two years. I now want to read more about the circadian rhythm. Tell me if you know of any interesting studies!