Stress hormone helps control the circadian rhythm of brain cells

November 8, 2019

Science Daily/University of Copenhagen The Faculty of Health and Medical Sciences

Researchers have shown how the brain's circadian rhythm in rats is, among other things, controlled by the stress hormone corticosterone -- in humans called cortisol. This has been shown by means of a completely new method in the form of implanted micropumps.

As day turns into night, and night turns into day, the vast majority of living organisms follow a fixed circadian rhythm that controls everything from sleep needs to body temperature.

This internal clock is found in everything from bacteria to humans and is controlled by some very distinct hereditary genes, known as clock genes.

In the brain, clock genes are particularly active in the so-called suprachiasmatic nucleus. It sits just above the point where the optic nerves cross and sends signals to the brain about the surrounding light level. From here, the suprachiasmatic nucleus regulates the rhythm of a number of other areas of the body, including the cerebellum and the cerebral cortex.

However, these three areas of the brain are not directly linked by neurons, and this made researchers at the University of Copenhagen curious. Using test rats, they have now demonstrated that the circadian rhythm is controlled by means of signalling agents in the blood, such as the stress hormone corticosterone.

'In humans, the hormone is known as cortisol, and although the sleep rhythm in rats is the opposite of ours, we basically have the same hormonal system', says Associate Professor Martin Fredensborg Rath of the Department of Neuroscience.

He explains that recent years have seen an increasing, scientific focus on research on clock genes, one reason being that previous research on clock genes have found a correlation between depression and irregularities in the body's circadian rhythms.

New Method with Medical Micropumps

In the study with the stress hormone corticosterone, the researchers removed the suprachiasmatic nucleus in a number of rats. As expected, this removed the circadian rhythm of the animals.

Among other things, the body temperature and activity level of the rats went from circadian oscillations to a more constant state. The same was true of the otherwise rhythmic hormone production.

However, the circadian rhythm of the cerebellum was restored when the rats were subsequently implanted with a special programmable micropump, normally used to dose medication in specific quantities.

In this case, however, the researchers used the pump to emit carefully metered doses of corticosterone at different times of the day and night, similar to the animals' natural rhythm.

'Nobody has used these pumps for anything like this before. So technically, we were onto something completely new', says Martin Fredensborg Rath.

For that reason, the researchers spent the best part of a year carrying out a large number of control tests to ensure that the new method was valid.

Interaction Between Neurons and Hormones

As mentioned, the new method paid off. With the artificial corticosterone supplement, researchers were again able to read a rhythmic activity of clock genes in the cerebellum of the rats, even though their suprachiasmatic nucleus had been removed.

'This is hugely interesting from a scientific point of view, because it means that we have two systems -- the nervous system and the hormonal system -- that communicate perfectly and influence one another. All in the course of a reasonably tight 24-hour programme', says Martin Fredensborg Rath.

With the test results and the new method in the toolbox, the researchers' next step is to study other rhythmic hormones in a similar manner, including hormones from the thyroid gland.

https://www.sciencedaily.com/releases/2019/11/191108102850.htm

Newly discovered neural pathway processes acute light to affect sleep

Different pathways process long-term circadian rhythms and short-term exposure to light

July 19, 2019

Science Daily/Northwestern University

Either to check the time or waste time, people often look at their smartphones after waking in the middle of the night.

While this acute burst of light does make it more difficult to fall back to sleep, a new Northwestern University study reports that it won't interfere with the body's overall circadian rhythms.

For the first time, researchers directly tested how short pulses of light are processed by the brain to affect sleep. They discovered that separate areas of the brain are responsible for short pulses versus long-term exposure to light. This finding challenges the widely accepted, long-held belief that all light information is relayed through the brain's suprachiasmatic nucleus (SCN), which synchronizes the body's sleep/wake cycles.

"Prior to the widespread use of electricity, our exposure to light and darkness occurred in a very predictable pattern," said Northwestern's Tiffany Schmidt, who led the study. "But light has become very cheap. We all have smartphones, and their screens are very bright. We're all getting exposed to light at the wrong times of day. It's becoming more important to understand how these different types of light information are relayed to the brain."

The paper will publish July 23 in the journal eLife. Schmidt is an assistant professor of neurobiology in Northwestern's Weinberg College of Arts and Sciences. The study was carried out in collaboration with the laboratories of Fred Turek, the Charles and Emma Morrison Professor of Neurobiology in Weinberg, and Samer Hattar, section leader at the National Institute of Mental Health.

After light enters the eye, specialized neurons called intrinsically photosensitive retinal ganglion cells (ipRGCs) carry the light information to the brain. Before Northwestern's study, researchers widely believed that all light information went through the SCN, a densely packed area in the hypothalamus known as the body's "circadian pacemaker."

"Light information comes into the SCN, and that's what synchronizes all of the body's clocks to the light/dark cycle," Schmidt said. "This one master pacemaker makes sure everything is in sync."

To conduct the study, Schmidt and her team used a genetically modified mouse model that only had ipRGCs projecting to the SCN -- but no other brain regions. Because mice are nocturnal, they fall asleep when exposed to light. The mice in the experiment, however, stayed awake when exposed to short pulses of light at night. The mice's body temperature, which also correlates to sleep, also did not respond to the short-term light.

The mice maintained a normal sleep/wake cycle and normal rhythms in their body temperature, suggesting that their overall circadian rhythms remained intact. This helps explain why one night of restless sleep and smartphone gazing might make a person feel tired the following day but does not have a long-term effect on the body.

"If these two effects -- acute and long-term light exposure -- were driven through the same pathway, then every minor light exposure would run the risk of completely shifting our body's circadian rhythms," Schmidt said.

Now that researchers know that the light-response system follows multiple pathways, Schmidt said more work is needed to map these pathways. For one, it is still unknown what area of the brain is responsible for processing acute light.

After more is known, then researchers might understand how to optimize light exposure to increase alertness in those who need it, such as nurses, shift workers and emergency personnel, while mitigating the harmful effects of a wholesale shift in circadian rhythms.

"Light at the wrong time of day is now recognized as a carcinogen," Schmidt said. "We want people to feel alert while they are exposed to light without getting the health risks that are associated with shifted circadian rhythms, such as diabetes, depression and even cancer."

https://www.sciencedaily.com/releases/2019/07/190719135543.htm