Shedding light on the happy hormone

Researchers led by Osaka University developed a novel fluorescent sensor to detect and monitor levels of the neuropeptide oxytocin, also known as the “happy hormone.” The OT sensor facilitated the successful measurement of OT dynamics in the brains of living animals and may serve as a foundation for the development of therapeutics for the treatment of neurological disorders such as autism and schizophrenia.

Fig. 1 Summary of this research
The problem in this research field(left) and approaches to address the problem (center, right) are described. In this study, we developed a fluorescent sensor for real-time measurement of brain oxytocin dynamics in living mice. This new tool will pave the way for the elucidation of how oxytocin acts on the brain during a variety of biological processes.

Researchers led by Osaka University engineer a fluorescent sensor to visualize the release of the neuropeptide oxytocin, also known as the “happy hormone,” in living animals

 Osaka, Japan – Twinkling lights make a city view all the more beautiful at night, and may evoke feelings of romance and happiness. But what do those feelings look like inside the brain? Recently, researchers in Japan demonstrated that the power of light may also be harnessed to monitor release of the “happy hormone” oxytocin (OT), a peptide produced in the brain that is associated with feelings of happiness and love. 

In a new study published in Nature Methods, researchers led by Osaka University reported their development of a novel fluorescent sensor for the detection of OT in living animals. OT plays an important role in a variety of physiological processes, including emotion, appetite, childbirth, and aging.

 Impairment of OT signaling is thought to be associated with neurological disorders such as autism and schizophrenia, and a better understanding of OT dynamics in the brain may provide insight into these disorders and contribute to potential avenues of treatment. Previous methods to detect and monitor OT have been limited in their ability to accurately reflect dynamic changes in extracellular OT levels over time. Thus, the Osaka University-led research team sought to create an efficient tool to visualize OT release in the brain.

 “Using the oxytocin receptor from the medaka fish as a scaffold, we engineered a highly specific, ultrasensitive green fluorescent OT sensor called MTRIAOT,” says lead author of the study, Daisuke Ino. “Binding of extracellular OT leads to an increase in fluorescence intensity of MTRIAOT, allowing us to monitor extracellular OT levels in real time.”

 The research team performed cell culture analyses to examine the performance of MTRIAOT. Subsequent application of MTRIAOT in the brains of living animals allowed for the successful measurement of OT dynamics using fluorescence recording techniques.

 “We examined the effects of potential factors that may affect OT dynamics, including social interaction, anesthesia, feeding, and aging,” says Ino. 

Fig. 2 Measurement of brain OT dynamics with MTRIAOT
Brain OT responses induced by acute-stress stimulus (left), by social interaction (center), and during daily behaviors (right). Our measurements revealed that the temporal profiles of OT signals were highly variable and depended on the behavioral context of the mouse.

The research team’s analyses revealed variability in OT dynamics in the brain that was dependent on the behavioral and physical conditions of the animals. Interactions with other animals, exposure to anesthesia, food deprivation, and aging all corresponded with specific patterns of brain OT levels.

 These findings indicate that MTRIAOT may serve as a useful tool to enhance our understanding of OT dynamics in the brain. Because abnormalities in OT signaling are thought to be associated with mental disorders, this tool may pave the way for the development of novel therapeutics for the treatment of these diseases. Additionally, the researchers found that the MTRIA backbone used to engineer the OT sensor may also serve as a scaffold to create sensors for other important brain hormones and neurotransmitters.

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 The article, “A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain,” was published in Nature Methods at DOI: https://www.nature.com/articles/s41592-022-01597-x

About Osaka University

Osaka University was founded in 1931 as one of the seven imperial universities of Japan and is now one of Japan's leading comprehensive universities with a broad disciplinary spectrum. This strength is coupled with a singular drive for innovation that extends throughout the scientific process, from fundamental research to the creation of applied technology with positive economic impacts. Its commitment to innovation has been recognized in Japan and around the world, being named Japan's most innovative university in 2015 (Reuters 2015 Top 100) and one of the most innovative institutions in the world in 2017 (Innovative Universities and the Nature Index Innovation 2017). Now, Osaka University is leveraging its role as a Designated National University Corporation selected by the Ministry of Education, Culture, Sports, Science and Technology to contribute to innovation for human welfare, sustainable development of society, and social transformation.

Website: https://resou.osaka-u.ac.jp/en

 

Published: 22 Sep 2022

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Global Strategy Unit

1-1 Yamadaoka, Suita,Osaka 565-0871, Japan

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Funding information:

Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Japan Science and Technology Agency
Takeda Science Foundation
LOTTE Foundation
Research Foundation for Opto-Science and Technology
Konica Minolta Science and Technology Foundation
Salt Science Research Foundation
Hokuriku Bank