The findings, reported in the October 6 issue of the journal Cell, may have implications for human studies seeking to understand innate differences in people's tolerance for alcohol. The research was supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services.
The study was authored by Adrian Rothenfluh, Ph.D., and colleagues in the laboratory of Ulrike Heberlein, Ph.D., at UCSF, in collaboration with researchers at the Ernest Gallo Clinic & Research Center. The scientists examined the behavior of fruit flies (Drosophila) exposed to alcohol. Ordinarily, at low doses of alcohol fruit flies increase their activity, while high doses have a sedative effect. However, the researchers found some fruit flies were much more resistant to alcohol sedation. These flies continued to move about much longer than typical fruit flies exposed to the same amount of alcohol. The scientists subsequently identified key differences in a particular gene associated with this behavior. The mutation also altered the flies' sensitivity to cocaine and nicotine as well. Because this gene variant affected the behavioral response to substances of abuse, the researchers dubbed it white rabbit--a reference to the title of a 1960s song about drug-induced changes.
"This study describes key molecular pathways and gene interactions that control alcohol sensitivity," said NIAAA Director Ting-Kai Li, M.D. "These significant clues about the fruit fly's behavioral response may translate into useful tools to advance the search for human genes involved in sensitivity to alcohol. Insights about sensitivity, or acute tolerance, are especially important because we know that people who are less sensitive to alcohol's impact are at greater risk for becoming alcohol dependent," he said.
The researchers exposed fruit flies to vaporized alcohol and monitored their behavior and motion patterns with sensitive tracking instruments. They isolated the flies that were less sensitive to alcohol's sedative effects. By breeding subsequent populations of mutant flies, the scientists identified the particular genetic mutation.
The researchers further showed that the white rabbit mutation disrupted the function of the RhoGAP18B gene. They also isolated a number of gene variants of RhoGAP18B, each of which had a distinctly different effect on the response to alcohol. Manipulating these genetic variants, the researchers generated flies with greater and lesser sensitivity to alcohol's sedative and stimulant effects.
The research team also detailed how signaling proteins encoded by the RhoGAP18B gene variants played an important role in reorganizing components of the adult fruit fly's central nervous system, which in turn affected the flies' behavior. Dr. Rothenfluh said the research team concluded that the RhoGAP18B gene is intimately involved in regulating behavioral responses to alcohol exposure.
The findings have implications for researchers seeking corresponding genes and molecular pathways in other animal models and humans. Antonio Noronha, Ph.D., director of NIAAA's Division of Neuroscience and Behavior, said, "If we can characterize similar genetic differences and neurobehavioral responses that underlie acute tolerance in humans, that could potentially provide new targets for the development of drugs to treat alcohol dependence."
Tag it EASI – a new method for accurate protein analysis
20.06.2018 | Max-Planck-Institut für Biochemie
How to track and trace a protein: Nanosensors monitor intracellular deliveries
19.06.2018 | Universität Basel
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences
20.06.2018 | Materials Sciences