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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

Figure 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.

 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 MTRIA_OT,” says lead author of the study, Daisuke Ino. “Binding of extracellular OT leads to an increase in fluorescence intensity of MTRIA_OT, allowing us to monitor extracellular OT levels in real time.”

The research team performed cell culture analyses to examine the performance of MTRIA_OT. Subsequent application of MTRIA_OT 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.

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 MTRIA_OT 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

Summary: 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.

Tweet : Shedding light on happiness in the brain? Researchers develop a fluorescent sensor to monitor “happy hormone” oxytocin.

Primary Keyword: Health and medicine
Additional Keywords: Oxytocin, Neuropeptides, Hormones, Neurochemistry, Neurophysiology, Neurological Disorders

Method of Research: Imaging analysis

Subject of Research: Animals

Figure 2. Measurement of brain OT dynamics with MTRIA_OT
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.

Title: “A fluorescent sensor for real-time measurement of extracellular oxytocin dynamics in the brain”
Journal: Nature Methods
Authors:  Daisuke Ino, Yudai Tanaka, Hiroshi Hibino, and Masaaki Nishiyama
DOI: 10.1038/s41592-022-01597-x

Funded by: 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.