Drinking blocks a chemical that promotes attention

December 02, 2020

SAN ANTONIO, Texas, USA - In a new paper, researchers from The University of Texas Health Science Center at San Antonio (UT Health San Antonio) report brain chemistry that may contribute to why drinkers have difficulty paying attention while under the influence.

The work is funded by generous support from the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation and by grants from the National Institute on Alcohol Abuse and Alcoholism and the National Institute of Mental Health. Findings were published Dec. 2 in Nature Communications.

"When we want to focus on something, or when we stand up from a chair and become active, a brain stem nucleus releases a chemical called norepinephrine. Acute exposure to alcohol inhibits this signal in the brain," said senior author Martin Paukert, MD, assistant professor of cellular and integrative physiology at UT Health San Antonio. When attention is needed for a task, norepinephrine is secreted by a brain structure called the locus coeruleus. Scientists previously did not understand well what happens next, but Dr. Paukert and the team showed that the norepinephrine attaches to receptors on cells called Bergmann glia. This leads to a calcium rise in these cells.

Bergmann glia are astrocytes (caretaker or supporting cells) in the cerebellum, a region near the brain stem. "To our knowledge, this paper is the first description that norepinephrine in mammals directly binds to receptors on the Bergmann glia and activates them through calcium elevation," Dr. Paukert said.

The researchers focused on the Bergmann glia but also demonstrated that the same phenomenon occurs in cortical astrocytes. "Most likely vigilance-dependent astrocyte calcium activation is inhibited throughout the brain by acute alcohol intoxication," Dr. Paukert said.

Persons under the influence are off-balance when they walk. The researchers expected to find that the inhibition of calcium rise in Bergmann glia would also explain this. It didn't. "The calcium elevation in Bergmann glia is not critical for motor coordination, which is somewhat surprising because the cerebellum is classically known for its role in motor control," Dr. Paukert said. "However, our findings are in line with current suggestions that the cerebellum also plays critical roles in non-motor functions, and that astrocytes are not only supporting basic brain maintenance, but they may actively participate in cognitive function."

The coauthors included Manzoor Bhat, PhD, professor and chairman of cellular and integrative physiology at UT Health San Antonio. "The beauty of the studies reported by Paukert and coauthors is that they have been conducted in real time in living and breathing animals using state-of-the-art technologies," Dr. Bhat said. "The findings will open up new avenues of defining the brain circuits that ultimately determine the state of alertness, and how chemicals that interfere with those circuits essentially dampen this inherent vigilance system of the brain."

The team utilized a technique called two-photon imaging to study specialized mice obtained from collaborators at Johns Hopkins University and Heidelberg University.
-end-
Ethanol abolishes vigilance-dependent astroglia network activation in mice by inhibiting norepinephrine release

Liang Ye, Murat Orynbayev, Xiangyu Zhu, Eunice Y. Lim, Ram R. Dereddi, Amit Agarwal, Dwight E. Bergles, Manzoor A. Bhat and Martin Paukert

First published: Dec. 2, 2020, Nature Communications

https://doi.org/10.1038/s41467-020-19475-5

The Long School of Medicine at The University of Texas Health Science Center at San Antonio is named for Texas philanthropists Joe R. and Teresa Lozano Long. The school is the largest educator of physicians in South Texas, many of whom remain in San Antonio and the region to practice medicine. The school teaches more than 900 students and trains 800 residents each year. As a beacon of multicultural sensitivity, the school annually exceeds the national medical school average of Hispanic students enrolled. The school's clinical practice is the largest multidisciplinary medical group in South Texas with 850 physicians in more than 100 specialties. The school has a highly productive research enterprise where world leaders in Alzheimer's disease, diabetes, cancer, aging, heart disease, kidney disease and many other fields are translating molecular discoveries into new therapies. The Long School of Medicine is home to a National Cancer Institute-designated cancer center known for prolific clinical trials and drug development programs, as well as a world-renowned center for aging and related diseases.

The University of Texas Health Science Center at San Antonio, also referred to as UT Health San Antonio, is one of the country's leading health sciences universities and is designated as a Hispanic-Serving Institution by the U.S. Department of Education. With missions of teaching, research, patient care and community engagement, its schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have graduated more than 37,000 alumni who are leading change, advancing their fields, and renewing hope for patients and their families throughout South Texas and the world. To learn about the many ways "We make lives better®," visit http://www.uthscsa.edu.

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University of Texas Health Science Center at San Antonio

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