Tag: circadian rhythm

Categories : NeurologyTags :

Study Explores the Circadian Rhythm Control Centre

On By ModernMedia
Woman sleeping with an alarm clock on bedside. Photo by cottonbro from Pexels

Researchers in Japan have offered new insights into how the brain’s circadian rhythm control centre regulates behaviour.

Circadian rhythms are a force in the background that shapes many human behaviours such feeling tired and falling asleep, as well as influencing our health. Michihiro Mieda and his team at Kanazawa University in Japan are researching just how the brain’s circadian rhythm control centre regulates behaviour.

The control centre, known as the superchiasmatic nucleus, or SCN, contains many types of neurons that transmit signals using the molecule GABA, but little is known about how each type contributes to our bodily rhythms. In this most recent study, the researchers focused on GABA neurons that produce arginine vasopressin, a hormone that regulates kidney function and blood pressure in the body, and which the team recently showed is also involved in the regulation of the interval of rhythms produced by the SCN.

To examine the function of these neurons separate to all others, the researchers first deleted a gene in mice which was needed for GABA signaling between neurons, but only in vasopressin-producing SCN neurons. “We removed a gene that codes for a protein that allows GABA to be packaged before it is sent to other neurons,” explained Mieda. “Without packaging, none of the vasopressin neurons could send out any GABA signals.”

Thus, these neurons could not use GABA to communicate with the rest of the SCN anymore. The mice showed longer periods of activity, beginning activity earlier and ending activity later than control mice, a simple enough result. It might seem that losing the packaging gene in the neurons disrupted the molecular clock signal but the result was not so simple. Closer examination deepened the mystery as the molecular clock seemed to progress unhindered.
Using calcium imaging, the researchers examined the clock rhythms within the vasopressin neurons. They found that while the rhythm of activity matched the timing of behaviour in control mice, this relationship was disturbed in the mice with missing GABA transmission in the vasopressin neurons. The rhythm of SCN output, ie SCN neuronal electrical activity, in the modified mice had the same irregular rhythm as their behaviour.

“Our study shows that GABA signaling from vasopressin neurons in the suprachiasmatic nucleus help fix behavioral timing within the constraints of the molecular clock,” concluded Mieda.

Source: News-Medical.Net

Journal reference: Maejima, T., et al. (2021) GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior. PNAS. doi.org/10.1073/pnas.2010168118.

Categories : Diseases, Syndromes and ConditionsTags :

Night Shifts Increase Risk of Infection

On By ModernMedia

Shift working and irregular working hours can affect our health and disrupt immune response, especially in men, according to new research from the University of Waterloo.

These health-related issues occur because the body’s circadian rhythm can be disrupted by inconsistent changes in the sleep-wake schedule and feeding patterns often caused by shift work. To study this, researchers at Waterloo developed a mathematical model to investigate how a disruption in the circadian clock affects the immune system in fighting off illness.

“Because our immune system is affected by the circadian clock, our ability to mount an immune response changes during the day,” said Anita Layton, professor of Applied Mathematics, Computer Science, Pharmacy and Biology at Waterloo. “How likely are you to fight off an infection that occurs in the morning than midday? The answer depends on whether you are a man or a woman, and whether you are among [the] quarter of the modern-day labor force that has an irregular work schedule.”

The researchers created new computational models, separately for men and women, which simulate the interplay between the circadian clock and the immune system. The model is composed of the core clock genes, their related proteins, and the regulatory mechanism of pro- and anti-inflammatory mediators. By adjusting the clock, the models can simulate male and female shift-workers.

The researchers’ simulation results demonstrate that the immune response varies with the time of infection. The model simulation indicates that the time just before people go to sleep is the “worst” time to get an infection. At this point during the day, the human body is least prepared to produce the pro- and anti-inflammatory mediators needed during an infection. An individual’s sex also impacts the effect significantly.

“Shift work likely affects men and women differently,” said Stéphanie Abo, a PhD candidate in Waterloo’s Department of Applied Mathematics. “Compared to females, the immune system in males is more prone to overactivation, which can increase their chances of sepsis following an ill-timed infection.”

Source: Medical Xpress

More information: Stéphanie M. C. Abo et al. Modeling the circadian regulation of the immune system: Sexually dimorphic effects of shift work, PLOS Computational Biology (2021). DOI: 10.1371/journal.pcbi.1008514

Categories : Cancer Diet and NutritionTags :

Breast Cancer in Mice Inhibited by Restricted Feeding Times

On By ModernMedia

Restricting calorie intake to an eight-hour window coinciding with physical activity reduced breast cancer risk in female mouse models.

Researchers from University of California San Diego School of Medicine, Moores Cancer Center and Veterans Affairs San Diego Healthcare System (VASDSH) found that the restricted feeding times, which are kind of circadian rhythm-linked intermittent fasting, enhanced metabolic health and tumour circadian rhythms in female mice with obesity-driven postmenopausal breast cancer. Breast cancer is the second most common cancer in US women, after skin cancer.

“Previous research has shown that obesity increases the risk of a variety of cancers by negatively affecting how the body reacts to insulin levels and changing circadian rhythms,” explained senior author Nicholas Webster, PhD. professor at UC San Diego School of Medicine and senior research career scientist at VASDSH. “We were able to increase insulin sensitivity, reduce hyperinsulinemia, restore circadian rhythms and reduce tumor growth by simply modifying when and for how long mice had access to food.”

Female mouse models mimicking postmenopausal hormone conditions were used to investigate if time-restricted feeding of obese mice affected the tumour growth and development, and reduced metastasis to the lungs. The mice were split into three groups, one with constant access to food, one with access for eight hours at night when they have the greatest activity, and the last was fed an unrestricted low-fat diet.

Obesity and menopause disrupt the circadian rhythm, with increased risk of insulin resistance and thereby chronic diseases such as cancer. A number of cancers are known to be associated with insulin resistance, such as breast cancer and pancreatic cancer. High insulin levels in obese mice drive tumour growth. Artificially increasing insulin levels has been shown to accelerate tumour growth whilst lowering them is similar to the effect of limiting eating.
Manasi Das, PhD, postdoctoral fellow in the Webster lab and first author, said: “Time-restricted eating has a positive effect on metabolic health and does not trigger the hunger and irritability that is associated with long-term fasting or calorie restriction. Through its beneficial metabolic effects, time-restricted eating may also provide an inexpensive, easy to adopt, but effective strategy to prevent and inhibit breast cancer without requiring a change in diet or physical activity.”

Webster believes that time-restricting eating warrants further investigations as it may present a way to reduce breast cancer risk, or that of cancer in general.

“The increase in risk of breast cancer is particularly high in women who are overweight and have been through menopause. For this reason, doctors may advise women to adopt weight loss strategies to prevent tumor growth,” said Das. “Our data suggests that a person may benefit from simply timing their meals differently to prevent breast cancer rather than changing what they eat.”

Source: Medical Xpress

Journal information: Manasi Das et al. Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models, Nature Communications (2021). DOI: 10.1038/s41467-020-20743-7