The release of norepinephrine into the cells is reduced, which leads to a cascade of effects.
In a new article, researchers from the University of Texas Health Science Center at San Antonio (UT Health San Antonio) report on the brain chemistry that may contribute to why drinkers struggle to pay attention while under the influence.
The work is funded by generous support from the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation, and grants from the National Institute on Alcohol Abuse and Alcoholism and the National Institute of Mental Health. The results were published today (December 2, 2020) in Nature communication.
“When we want to focus on something, or when we get up from a chair and take action, a core of the brainstem releases a chemical called norepinephrine. Acute alcohol exposure inhibits this signal in the brain, ”said lead author Dr. Martin Paukert, Assistant Professor of Cellular and Integrative Physiology at UT Health in San Antonio. When a task requires attention, norepinephrine is secreted by a brain structure called the locus coeruleus. So far, scientists haven’t got a very good understanding of what happens next, but Dr. Paukert and the team have shown that norepinephrine binds to receptors on cells called Bergmann’s glia. This leads to an increase in calcium in these cells.
Martin Paukert, MD from the Long School of Medicine of Joe R. and Teresa Lozano at the University of Texas Health Science Center at San Antonio studies astroglial cells and how they interact with neurons in the brain. Photo credit: UT Health San Antonio
Bergmann glia are astrocytes (caretaker or support cells) in the cerebellum, a region near the brain stem. “To the best of our knowledge, this paper is the first description that norepinephrine in mammals binds directly to receptors on Bergmann’s glia and activates them by increasing calcium,” said Dr. Paukert.
The researchers focused on Bergmann’s glia but also showed that the same phenomenon occurs in cortical astrocytes. “Most likely the alertness-dependent calcium activation of astrocytes throughout the brain is inhibited by acute alcohol intoxication,” said Dr. Paukert.
Individuals under the influence have become unbalanced while walking. The researchers expected that inhibiting the rise in calcium in Bergmann’s glia would explain this as well. It was not like that. “The calcium elevation in Bergmann’s glia is not critical to motor coordination, which is somewhat surprising as the cerebellum is classically known for its role in motor control,” said Dr. Paukert. “Our results, however, agree with the current proposals that the cerebellum also plays a crucial role in non-motor functions and that astrocytes not only support the basic maintenance of the brain, but can also actively participate in cognitive function.”
Co-authors included Manzoor Bhat, PhD, professor and chairman of cellular and integrative physiology at UT Health San Antonio. “The nice thing about the studies reported by Paukert et al. Is that they were done in real time with living and breathing animals using cutting-edge technology,” said Dr. Bhat. “The results will open up new avenues for defining the brain circuits that ultimately determine the state of vigilance and how chemicals that disrupt these circuits essentially dampen this brain’s inherent vigilance system.”
The team used a technique called two-photon imaging to examine specialized mice obtained from staff at Johns Hopkins University and Heidelberg University.
Reference: “Ethanol abolishes the alertness-dependent activation of the astroglia network in mice by inhibiting the release of norepinephrine” by Liang Ye, Murat Orynbayev, Xiangyu Zhu, Eunice Y. Lim, Ram R. Dereddi, Amit Agarwal, Dwight E. Bergles, Manzoor A. Bhat and Martin Paukert, December 2, 2020, Communication with nature.
DOI: 10.1038 / s41467-020-19475-5
Funding: Robert J. Kleberg Jr. and Helen C. Kleberg Foundation, National Institute on Alcohol Abuse and Alcoholism, National Institute for Mental Health.
