Research Highlights

Research News
Friday, June 24, 2016
Both humans and animals experience stress. Ideally, stress serves as a survival tool, allowing organisms to adapt and overcome adversity in an unpredictable environment. As a result, higher-order animals have developed complex systems to perceive, react to, and adapt to psychological stress, ensuring that they can respond to environmental dangers that might harm or kill them. But for some, the response to stress can go awry, and what started as a natural response to a changing environment can ultimately become a chronic disease such as depression, anxiety disorder, or posttraumatic stress disorder (PTSD). A recent review in Nature Neuroscience explores how innovative findings in animals can advance our understanding of stress-related mental disorders in humans.
The review, written by Dr. Ahmad Hariri, Duke University, and Dr. Andrew Holmes, NIAAA Laboratory of Behavioral and Genomic Neuroscience, notes that the neural circuits and underlying genes that control the stress response are similar across species. Hence, studies in animals (known as preclinical studies) have revealed much about the systems that play a central role in psychological stress, such as the hypothalamic–pituitary–adrenal axis, a complex interaction between three endocrine glands. Based on preclinical work, scientists also have an important understanding of how the brain perceives and processes stressful experiences. Across species, the amygdala, hippocampus, and prefrontal cortex work together to play a critical role in both short-term and long-term response to stress. Using animal models, scientists have also been able to identify genetic variants that contribute to stress-related disorders. These candidate genes could help identify people at risk for such disorders and provide possible targets for developing treatments.
Preclinical models have been developed for a wide range of disorders. The authors note that “translational stress research is thus positioned to be a standard bearer for the charge toward the recasting of mental illness as manifestations of disordered brain circuits and the behavioral processes they subserve.”
Hariri, A., and Holmes, A. Finding translation in stress research. Nature Neuroscience 18(10):1347–1352, 2015. PMID: 26404709

Reprinted from the NIAAA Spectrum, Volume 8, Issue 2, June 2016.

Research News
Thursday, November 10, 2016

Researchers have identified a blood test that may help predict how severely a baby will be affected by alcohol exposure during pregnancy, according to a study published November 9 in the journal PLOS ONE.

The study authors, from the University of California San Diego School of Medicine, Texas A&M College of Medicine and the Omni-Net Birth Defects Prevention Program in Ukraine, say the findings could facilitate early intervention to improve the health of infants and children who were prenatally exposed to alcohol, according to a UC San Diego news release.

Co-authors of the paper include: Sridevi Balarama, and Alexander M. Tseng, Texas A&M Health Science Center; and Lyubov Yevtushok, and Natalya Zymak-Zakutnya, Omni-Net Ukraine Birth Defects Prevention Program.

Funding for this research came, in part, from the National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism (grant numbers U01AA014835, U24AA014811, R01AA013440) and the Collaborative Initiative on Fetal Alcohol Spectrum Disorders.

Read the full text of the UC San Diego news release



Research News
Monday, July 18, 2016
You may be familiar with how doctors use pictures from magnetic resonance imaging machines, better known as MRIs, to diagnose injuries and other health problems. But did you know that NIAAA scientists have another technology that harnesses the power of strong magnets to study receptors in the brain that could be targets for alcohol therapies? NIAAA’s Intramural Section on Nuclear Magnetic Resonance (NMR) uses an NMR spectrometer, which utilizes a strong magnetic field and radio waves to delineate the structure of brain proteins and of the membranes they are embedded in, allowing scientists to design selective new drug molecules that bind to these receptors.
Unlike an MRI machine, an NMR spectrometer is not used directly on patients, but rather on very small samples, which are usually reconstituted highly purified protein-coupled membrane receptors, but could also be a preparation of natural cell membranes. These samples model the highly variable composition of a human cell membrane, allowing scientists to study its properties, including the function of certain receptors. The NMR spectrometer provides detailed information about the shape, dynamics, and interactions of molecules, and has been used in NIAAA studies to deepen our understanding of how substances such as docosahexaenoic acid—an omega-3 fatty acid—interact with membrane receptors. Findings from NIAAA’s NMR studies have important implications for improving our understanding of human nutrition, including the influence of alcohol on the composition and function of membranes.

Laboratory of Membrane Biochemistry and Biophysics

Above, NIAAA scientists Drs. Olivier Soubias, Klaus Gawrisch, and Walter Teague (L-R) are pictured in the room that was specially constructed to house the “big magnet.” This device is powerful enough to resolve protein structures but is also so sensitive that it needs to be protected from temperature changes and vibrations in order to produce accurate data.


Reprinted from the NIAAA Spectrum, Volume 8, Issue 2, June 2016.

Research News
Wednesday, June 29, 2016
Dr. Bin Gao probes alcohol liver disease
Above: Dr. Bin Gao, Chief of the Laboratory of Liver Diseases in the Division of Intramural Clinical and Biological Research (DICBR), NIAAA. (Credit: NIH IRP)
The following is an excerpt from a web page feature from the National Institutes of Health (NIH) Intramural Research Program (IRP):
While many people may enjoy an occasional alcoholic beverage, excessive alcohol consumption causes adverse effects on the body and mind, including changes in mood and behavior, as well as damage to the liver, heart, and pancreas. Not all chronic alcohol users go on to develop advanced liver disease (ALD), but for the 30-40 percent of heavy drinkers who develop severe liver damage—such as alcoholic hepatitis, cirrhosis, and hepatocellular carcinoma (the most common type of liver cancer)—the current lack of effective treatment strategies is sobering.
“While there are effective drugs for other types of liver disease, such as viral hepatitis, the pathogenesis for alcoholic liver damage is still not clear, and there are no approved therapies for ALD,” explains Bin Gao, Ph.D., Chief of the Laboratory of Liver Diseases in the Division of Intramural Clinical and Biological Research at the National Institute on Alcohol Abuse and Alcoholism. “We’re working on multiple research projects at the cellular and molecular level to give us the foundational knowledge to change that.”
► Read the complete NIH IRP feature:
►Watch the NIH IRP video:
►Visit Dr. Gao's web page: Laboratory of Liver Diseases
Research News
Monday, June 27, 2016
Recent NIH-wide efforts to address sex differences in preclinical research underscore the importance of such issues to scientists who study alcohol addiction.
“In fact, animal models of alcohol addiction reveal significant differences between males and females,” says NIAAA Director George F. Koob, Ph.D., “but we have little data thus far to help us understand the neurobiological mechanisms for those differences.”
NIAAA’s increased emphasis on research in this area will be informed by a timely new review article, co-authored by Dr. Koob and Dr. Jill Becker of the University of Michigan, titled, “Sex Differences in Animal Models: Focus on Addiction.” Published in the April 2016 issue of the journal Pharmacological Reviews, the article discusses ways to think about and study sex differences in preclinical animal models.
“We use the framework of addiction to illustrate the importance of considering sex differences,” says Dr. Koob, “and we have outlined major quantitative, population, and mechanistic sex differences in the addiction domain. We also emphasize the need for new studies to help us understand those differences.”
Becker, J.B., and Koob, G.F. Sex differences in animal models: Focus on addiction. Pharmacological Reviews 68(2):242–263, 2016. PMID: 26772794