Sound of music: Ultrasound exposure improves depressive behavior in rodents

The effect of ultrasound waves on the function of the human brain has been the key focus of recent research, which has indicated its potential as an effective, non-invasive approach for the modulation of brain activity. While the effects of ultrasound exposure on consciousness and cognition have been extensively explored, little is known about its impact on emotional states such as depression. To add to it, there are limitations in our understanding of neural and molecular mechanisms that underpin emotions.

Fortunately, rats experience pleasant emotions in response to high-frequency ultrasound vocalizations (USVs), making them ideal model organisms to study mechanisms underlying depression.

To this end, a team of researchers led by Professor Akiyoshi Saitoh, including Professor Satoru Miyazaki, Assistant Professor Daisuke Yamada and Ms. Tsugumi Yamauchi from Tokyo University of Science, and Mr. Shoichi Nishino from FUJIMIC, Inc., delved deeper into understanding the effects of ultrasound exposure on depression, by conducting experiments on rats lacking olfactory lobes—organs that regulate neurotransmission. These “olfactory bulbectomized (OB)” rats undergo changes in neurotransmitters, endocrine secretions, and behavior, which are similar to those observed in humans with depression.

Giving further insights into their study, Prof. Saitoh remarked, “Since studies on ultrasound exposure have been primarily conducted on human subjects, we needed to establish robust animal models to elucidate underlying mechanisms using invasive techniques. In our current study, we have used OB rats to study the effects of ultrasound on neural activity and behavior” Their study, published in Volume 33, Issue 10 of NeuroReport on July 6, 2022, is the first of its kind to demonstrate potential anti-depressant effects of ultrasound exposure in rats.

Initially, the team exposed wild type and OB rats to USV for 24 hours, following which they scored them for “hyperemotionality” (agitation and anxiety-like behavior) by studying their responses to getting attacked, getting startled, facing a struggle, and initiating a fight.

Next, they monitored plasma corticosterone (a hormone that is released in response to stress) levels in the blood samples of these rats. In addition, the team assessed anxiety-like behavior of the rodents using the elevated plus maze (EPM)—an approach which triggers behavioral anxiety in rats by exposing them to open spaces in a maze, and causes them to move to closed spaces.

Their findings revealed that OB rats exposed to USV had significantly lower hyperemotionality scores and lower plasma corticosterone levels than unexposed rats. Furthermore, in OB rats with a higher latency initially. i.e., higher inclination to reach the open areas of the maze, ultrasound exposure significantly decreased their latency. Similar effects were observed with a 50-kHz ultrasound frequency which was generated artificially.

This study provides novel evidence on the anti-depressant effects of ultrasound exposure in rodents. “Our findings suggest that OB rats may be a useful animal model for investigating the effects of ultrasound exposure and mechanisms of influence.”, exclaims Prof. Saitoh about the implications of the study.

He further adds, “Unlike drug therapy, ultrasound exposure is non-invasive and easy to use. An ultrasound based therapeutic device may therefore aid the treatment and prevention of mental disorders in patients while they go about their daily lives.”

Let’s hope that these results pave the way for developing ultrasound exposure therapy as a novel treatment to help patients cope with stress and psychiatric disorders.

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About The Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science through inculcating the love for science in researchers, technicians, and educators.
With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.

Website: https://www.tus.ac.jp/en/mediarelations/

About Professor Akiyoshi Saitoh from Tokyo University of Science
Dr. Akiyoshi Saitoh is a Professor in the Department of Pharmaceutical Sciences at Tokyo University of Science. His research interests include drug discovery pharmacology, neuroscience and behavioral pharmacology. The Saitoh research group led by him is currently developing animal models to understand human neural circuits. In the area of drug research, they are developing antidepressants, anxiolytics targeting opioid receptors, and antipsychotics. Additionally, they also study the psychological and neural effects of ultrasonic and electromagnetic waves. Dr. Saitoh has published over 100 peer-reviewed articles since starting out in the field of neuro-psychopharmacological science in 1994.