Potential to combat depression by restoring key brain rhythms found

Research Suggests Role of Gamma Oscillations in Future Therapy

new york, May 9, 2023 /PRNewswire/ — Led by researchers from NYU Grossmann School of Medicine and Szeged University Hungarya new study in mice and rats found that restoring specific signals in the brain regions that process smells can counteract depression.

Publication in magazines neuron online May 9th, research findings revolve around nerve cells (neurons) that “fire” or emit electrical signals to transmit information. Recent researchers have found that effective communication between brain regions requires groups of neurons to synchronize their activity patterns with joint silences followed by repeated periods of joint activity (oscillations). . One such rhythm, called ‘gamma’, repeats about 30 or more times per second and is an important timing pattern for encoding complex information that may contain emotion.

The cause is not well understood, but previous research has shown that depression is reflected in changes in gamma oscillations, electrophysiological markers of disease in brain regions that control smell, and is also linked to emotion. . These areas include the olfactory bulbs adjacent to the nasal cavity. It is believed to be the source and “conductor” of gamma oscillations throughout the brain.

To test this theory, the authors of the current study used genetic and cell signaling techniques to shut down bulb function and observed an associated increase in depression-like behavior in study rodents. and then reversed these behaviors using a device that boosts the gamma signal in the brain at a natural pace.

“Our experiments reveal a mechanistic link between deficits in gamma activity and behavioral depression in mouse and rat models of depression, suggesting that changes in olfactory and connected limbic signals It turned out to be similar to that seen in depressed patients,” said the corresponding study author. Antal Berenyi M.D. Ph.D., adjunct assistant professor in the Department of Neuroscience and Physiology at NYU Langone Health. “This study demonstrates the power of gamma-enhancing as a potential approach to combat depression and anxiety when available drugs are ineffective.”

Major depressive disorder is a common, severe mental illness that often resists medication, researchers say. The prevalence of this condition has increased dramatically since the beginning of the pandemic, 53 million new cases Estimate.

Gamma waves associated with emotions

Disease-causing alterations in the timing and intensity of gamma signals from the olfactory bulb to other brain regions of the limbic system, such as the piriform cortex and hippocampus, can be caused by infection, trauma, or drugs, and can be associated with emotions. may change. However, the research team is not sure why. One theory is that depression does not occur within the olfactory bulb, but through changes in outgoing gamma patterns to other brain targets.

Bulb removal represents an older animal model for the study of major depression, but the process can cause structural damage and cloud researchers’ view of disease mechanisms. Starting with a single engineered DNA strand encapsulated in a harmless virus, the research team designed a reversible method to avoid damage. When the virus was injected into neurons in the olfactory bulb of rodents, it caused the cells to build specific protein receptors. surface.

This allowed researchers to inject drugs into rodents. The drug spreads throughout the body, but only shuts down neurons in the bulb that are designed to have receptors that are sensitive to the designed drug. In this way, the researchers were able to selectively and reversibly turn off communication between brain regions of bulb partners. showed that it induced depressive behaviors not only during but also for several days thereafter.

To show the effects of the loss of gamma oscillations in the olfactory bulb, the research team used several standard rodent tests, including a measure of anxiety, one of the main symptoms of depression. Recognizing that animal models of human mental states are limited in the field, a battery of tests is used to measure depressive behaviors that have proven useful over time. I’m here.

Specifically, the test included the amount of time animals spent in open space (a measure of anxiety), whether they stopped swimming early when submerged (a measure of despair), and whether they stopped drinking sugar water (a measure of despair). less fun), and they refused to enter the maze (avoiding stressful situations).

The researchers then used a custom-made device that recorded natural gamma oscillations from the olfactory bulb and sent these pacing signals back to the rodent brain as closed-loop electrical stimulation. This device could either suppress or amplify gamma rays in healthy animals. Suppression of gamma oscillations in the olfactory lobe caused behavior similar to depression in humans. Furthermore, sending amplified olfactory bulb signals back to the brains of depressed rats restored normal gamma function in the limbic system and reduced depressive behavior by 40% (near normal).

“No one yet knows how gamma wave firing patterns translate into emotions,” said a senior study author. György Buzsáki, MD, PhDProfessor Biggs Department of Neuroscience and Physiology NYU Langone Health and its faculty Neuroscience Institute“As behavior changes, we will move forward to better understand this link in bulbs and the regions they connect to.”

Together with Berényi and Buzsáki, the study was led by Orin DevinskyMD, Professor and Director of the Department of Neurology at NYU Langone Comprehensive Epilepsy CenterBerényi is also a principal investigator in the Momentum Oscillatory Neuronal Networks Research Group at the Department of Physiology, University of Szeged. Hungarywith the first study authors Kun Lee and Yuichi Takeuchiand author Jale WangLevente Gellert, Livia Barsay, Rises Pedraza, Annette Nagy, Gabor Kosak, Jengie Horvath, Gabriela Kekesi, Magor Lorinz.Research author Shinya Nakai and Masahiro Ohsawa Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences Nagoya city ​​university JapanTakeuchi is also a faculty member of the Department of Physiology at the Graduate School of Medicine and Faculty of Pharmaceutical Sciences, Osaka City University. Hokkaido University of JapanAlso, the authors of the study are Shigeki Kato Kazuhito Kobayashi, Department of Molecular Genetics, Institute of Integrative Medical Sciences, Fukushima Medical University Japan.

Funding for this study was provided through a grant from the Hungarian National Agency for Research, Development and Innovation, the Momentum II program of the Hungarian Academy of Sciences. HungaryMinistry of Innovation and Technology HungaryMinistry of Human Capabilities, HungaryHungarian Science Research Fund, Hungarian Brain Research Program, European Union Horizon 2020 Research Innovation Program, Japan Society for the Promotion of Science, Japan Society for the Promotion of Science, Ministry of Education, Culture, Sports, Science and Technology of Japan, Japan Society for the Promotion of Medical Research and Development, and Kanae Foundation for the Promotion of Medical Science Supported by the Foundation, Life Sciences Foundation JapanTakeda Science Foundation, Japanese Neural Network Society, János Bólyai Fellowship.

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research link
URLs: https://www.cell.com/neuron/fulltext/S0896-6273(23)00298-2
DOI: 10.1016/j.neuron.2023.04.013

Source NYU Grossman School of Medicine and NYU Langone Health