UTSW neuroscientists identify cell type in the brain that controls body clock circadian rhythms

March 17, 2015

DALLAS - March 17, 2015 - UT Southwestern Medical Center neuroscientists have identified key cells within the brain that are critical for determining circadian rhythms, the 24-hour processes that control sleep and wake cycles, as well as other important body functions such as hormone production, metabolism, and blood pressure.

Circadian rhythms are generated by the suprachiasmatic nucleus (SCN) located within the hypothalamus of the brain, but researchers had previously been unable to pinpoint which of the many thousands of neurons in the region were involved in controlling the body's timekeeping mechanisms.

"We have found that a group of SCN neurons that express a neuropeptide called neuromedin S (NMS) is both necessary and sufficient for the control of circadian rhythms," said Dr. Joseph Takahashi, Chairman of Neuroscience and Howard Hughes Medical Institute (HHMI) Investigator at UT Southwestern, who holds the Loyd B. Sands Distinguished Chair in Neuroscience.

The findings, published in the journal Neuron, may offer important targets for future treatments of diseases and problems related to circadian dysfunction, which range from jet lag and sleep disorders to neurological problems such as Alzheimer's disease, as well as metabolism issues and psychiatric disorders such as depression.

Key studies in the 1970s revealed that the SCN communicates and coordinates cells throughout the body to control circadian rhythms, but the SCN contains many neurons with different expression patterns of neuropeptides and neurotransmitters.

"Which of these neurons are responsible for producing circadian rhythms was a major unanswered question in neurobiology. This study marks a significant advancement in our understanding of the body clock" said senior author Dr. Masashi Yanagisawa, Adjunct Professor of Molecular Genetics, former HHMI Investigator at UT Southwestern, and current Director of the World Premier International Institute for Integrative Sleep Medicine at the University of Tsukuba in Japan.

NMS is a neuropeptide - a protein made of amino acids that neurons, which are cells in the brain, use to communicate. Researchers created unique mouse models to determine that NMS-expressing neurons act as cellular pacemakers to regulate circadian rhythms. Specifically, the research team found that modulating the internal clock in just the NMS neurons altered the circadian period throughout the whole animal. In addition, the study provided new insights into the mechanisms by which light synchronizes body clock rhythms.

Dr. Takahashi identified and cloned the first mammalian gene -- called Clock--related to circadian rhythms. Since then, the Takahashi lab has determined that disruptions in the Clock and Bmal1 genes in mice can alter the release of insulin by the pancreas, resulting in diabetes, and they determined the 3-D structure of the CLOCK-BMAL1 protein complex, which are considered to be the batteries of the biological clock.

Dr. Yanagisawa first identified the important role that endothelin plays on the cardiovascular system, and later, with his discovery of orexin, showed that sleep/wakefulness is controlled by a single neuropeptide. His lab has since identified numerous receptors involved in the regulation of appetite and blood pressure, as well as other neuropeptides that play an important role in the regulation of energy metabolism, stress responses, emotions, and other functions.
-end-
The current research was supported by the National Institute of Health and the Howard Hughes Medical Institute.

Other UT Southwestern researchers involved include co-authors Ivan Lee, graduate student fellow in the Medical Scientist Training Program; Alexander Chang, former UT Southwestern graduate student; Manabu Manandhar, research technician in Molecular Genetics; Yongli Shan, postdoctoral researcher in Neuroscience; Junmei Fan and Mariko Izumo, senior research associates in Neuroscience; Yuichi Ikeda, former UT Southwestern postdoctoral researcher; Dr. Toshiyuki Motoike, Assistant Professor of Neuroscience; Shelley Dixon, lab manager in Neuroscience; and Jeffrey Seinfeld, former research technician.

About UT Southwestern Medical Center

UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering approximately 2,800, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to about 92,000 hospitalized patients and oversee approximately 2.1 million outpatient visits a year.

This news release is available on our home page at http://www.utsouthwestern.edu/home/news/index.html

UT Southwestern Medical Center

Related Blood Pressure Articles from Brightsurf:

Children who take steroids at increased risk for diabetes, high blood pressure, blood clots
Children who take oral steroids to treat asthma or autoimmune diseases have an increased risk of diabetes, high blood pressure, and blood clots, according to Rutgers researchers.

High blood pressure treatment linked to less risk for drop in blood pressure upon standing
Treatment to lower blood pressure did not increase and may decrease the risk of extreme drops in blood pressure upon standing from a sitting position.

Changes in blood pressure control over 2 decades among US adults with high blood pressure
National survey data were used to examine how blood pressure control changed overall among U.S. adults with high blood pressure between 1999-2000 and 2017-2018 and by age, race, insurance type and access to health care.

Transient increase in blood pressure promotes some blood vessel growth
Blood vessels are the body's transportation system, carrying oxygen and nutrients to cells and whisking away waste.

Effect of reducing blood pressure medications on blood pressure control in older adults
Whether the amount of blood pressure medications taken by older adults could be reduced safely and without a significant change in short-term blood pressure control was the objective of this randomized clinical trial that included 534 adults 80 and older.

Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.

Here's something that will raise your blood pressure
The apelin receptor (APJ) has been presumed to play an important role in the contraction of blood vessels involved in blood pressure regulation.

New strategy for treating high blood pressure
The key to treating blood pressure might lie in people who are 'resistant' to developing high blood pressure even when they eat high salt diets, shows new research published today in Experimental Physiology.

Arm cuff blood pressure measurements may fall short for predicting heart disease risk in some people with resistant high blood pressure
A measurement of central blood pressure in people with difficult-to-treat high blood pressure could help reduce risk of heart disease better than traditional arm cuff readings for some patients, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

Heating pads may lower blood pressure in people with high blood pressure when lying down
In people with supine hypertension due to autonomic failure, a condition that increases blood pressure when lying down, overnight heat therapy significantly decreased systolic blood pressure compared to a placebo.

Read More: Blood Pressure News and Blood Pressure Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.