Nav: Home

Novel role of microglia as modulators of neurons in the brain is discovered

September 30, 2020

Immune cells in the brain that act as scavengers to remove dying cells also play a potentially pivotal role in the regulation of behavior in both mice and humans, a research team from Mount Sinai has found. The newly identified function of the scavenger cells, known as microglia, to protect the brain from abnormal activation in health and disease has implications for treating behavioral abnormalities associated with neurodegenerative and inflammatory diseases in humans. The study was published September 30, 2020 in Nature.

"When we think about brain function, we typically think about how neurons control our thoughts and behavior," says Anne Schaefer, MD, PhD, Professor of Neuroscience, and Psychiatry, at the Icahn School of Medicine at Mount Sinai, and senior author of the study. "But the brain also contains large amounts of non-neuronal cells, including microglia, and our study puts a fresh spotlight on these cells as partners of neurons in the regulation of neuronal activity and behavior. We found that microglia can sense and respond to neuronal activation and provide negative feedback on excessive neuronal activity. This novel microglia-mediated mechanism of neuromodulation could play an important role in protecting the brain from disease."

Mount Sinai researchers identified the biochemical circuit that supports neuron-microglia communication. When neurons are active, they release a molecule called adenosine triphosphate (ATP). Microglia can sense extracellular ATP, and the compound draws them toward the active neurons. As the next step, the microglia break ATP down to generate adenosine, which then acts on adenosine receptors on the surface of active neurons to suppress their activity and prevent excessive activation.

"In inflammatory conditions and neurodegenerative diseases like Alzheimer's, microglia become activated and lose their ability to sense ATP and to generate adenosine," says Ana Badimon, PhD, a former student in the Schaefer Lab and first author of the study.

"This suggested to us that behavioral alterations associated with disease may be mediated, in part, by changes in microglial-neuron communication," adds Dr. Schaefer, who is also Co-Director of the Center for Glial Biology at The Friedman Brain Institute at the Icahn School of Medicine.

Dr. Schaefer describes the identification of the biochemical circuit that enables microglial control of neuronal responses as a potential "paradigm shift" in our understanding of how innate immune cells in the brain can contribute to behavior. This observation is particularly important, she adds, given the fact that microglia, while residing in the brain, are uniquely equipped to also respond to signals generated in the peripheral body. Microglia can therefore act as an interface between peripheral body changes, like a viral infection, and the brain by communicating these signals to neurons to modulate behavioral responses.

By shedding valuable light on the interaction of neurons and microglia, the study carries a number of practical implications for further research. They range from novel approaches of neuromodulation of normal behaviors by targeting microglia, to potential treatment of behavioral abnormalities associated with neurodegenerative diseases.

"The future promise of our study also lies in the identification of novel signals like ATP that will allow microglia to modulate the function of highly diverse neurons, including neurons controlling sleep or metabolism," says Dr. Schaefer. "We believe our work has the potential to add to our knowledge about the mechanisms of neuromodulation."
-end-
Other partners in the Mount Sinai-led study include California Institute of Technology, the Nagoya University Graduate School of Medicine in Japan, Kobe University Graduate School of Medicine in Japan, University of Minnesota, and Harvard Medical School.

The research described in this press release is funded in part by the National Institutes of Health, The Brain and Behavior Research Foundation, The Whitehall Foundation, and The Edward Mallinckrodt Jr. Foundation.

The National Institute on Aging, part of the National Institutes of Health, recently awarded the Icahn School of Medicine at Mount Sinai a $2.99 million grant (number RF1AG068558) that will enable Dr. Schaefer and colleagues to investigate the epigenetic mechanisms of systems microglia activation during aging and its contributions to neurodegenerative diseases.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality care--from prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty by U.S. News & World Report.

For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

The Mount Sinai Hospital / Mount Sinai School of Medicine

Related Neurons Articles:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.
Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.
A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.
Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.
Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.
Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.
The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.
Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.
How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.
A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.
More Neurons News and Neurons Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.