Astrocytes: The New Stars in Brain Health
A Revolution in The Treatment of ADHD, Depression, & Neurodegenerative Diseases
For nearly one hundred years, scientists have believed that neuromodulators like norepinephrine, dopamine, and serotonin orchestrate brain communication by influencing neurons—and by extension, that neurons are the nexus of brain health and disease.
But a groundbreaking new study has turned this assumption on its head.
The study has startling implications for attention, learning, memory, mental health, and neurodegenerative diseases. And it just may answer a longstanding conundrum in modern mental health: Why are antidepressants less effective than we’d like, and what can be done to remedy that?
Before we dive in to the study, let’s review two quick elements of brain anatomy that help to put this new discovery in perspective.
A Quick Primer in Neuron + Astrocyte Function
Since its inception, neuroscience has focused on neurons as the most important cellular component of the nervous system.
A single human brain contains a staggering 86 billion neurons—almost as many as there are stars in the milky way. And the synaptic connections between these neurons number in excess of 100 trillion.
Remarkable as these numbers are, neurons make up only 10 to 20 percent of the brain’s cellular population.
The remaining 80 to 90 percent are glial cells, which come in four types. One of these four is the astrocyte.
Until very recently, scientists thought that the star-shaped cells played a mere supporting role to neurons.
Part of this has to do with speed. Neurons communicate electrically and chemically. Their signaling can reach speeds of up to 100 meters per second, especially in myelinated neurons.
Astrocytes communicate using multiple mechanisms, including the release of chemical messengers called gliotransmitters and through calcium waves. But they communicate much more slowly—as much as 1/100th the speed of neurons.
This difference, in part, led researchers to focus on therapeutic drugs that target the activity neurons.
Until recently, that is.
This novel study upends decades of assumptions in neuroscience. And it opens up new therapeutic possibilities the treatment of anxiety, depression, ADHD, neurodegenerative disorders, and more.
The Link Between Norepinephrine and Depression
The study examined norepinephrine, a neuromodulator that influences neurons, neurotransmitters, and entire neural networks.
Norepinephrine plays a vital part in regulating arousal, attention, working memory, long-term cognitive function, the detection of sensory signals, and stress reactions. It also acts as a neurotransmitter in its own right, influencing the fight-flight-freeze response.
Norepinephrine also helps regulate metabolic processes such as glycogenesis and gluconeogenesis, two opposing pathways in glucose metabolism.
Norepinephrine remains one of the primary neuromodulators (alongside serotonin) used to treat depression.
Modern medicine uses selective norepinephrine reuptake inhibitors (SNRIs) and their serotonin counterparts (SNRIs) as a mainstay in the pharmacological treatment of depression, anxiety disorders, and pain syndromes. These medications increase the availability of norepinephrine by either inhibiting its reuptake or its breakdown.
Antidepressants help. They often take the edge of depression so people can make use of additional treatments like psychotherapy, movement, and immunomodulation.
Yet nearly half of all people with depression have no clinical response to two or more different antidepressants; they meet the criteria for treatment-resistant depression.
And modern medicine has limited strategies for treatment-resistant depression. These include optimizing dosages, augmenting treatment with mood stabilizers (like lithium) or antipsychotics, or non-standard treatments such as low-dose naltrexone (LDN), which can reduce inflammation in people with major depression.
For more about depression as an inflammatory illness, see this article.
For more about the social antecedents to depression, see this one.
Importantly, considerable speculation remains as to whether clinical responses to antidepressants match or exceed placebo, exercise, or psychotherapy.
Yet serotonin remains a key thread that weaves together multiple forms of antidepressant therapy, including ketamine and other psychedelics.
Enter the study.
The Study’s Exciting Results
Researchers had long suspected that astrocytes might be able to rearrange communication between neurons and, as a result, the flow of information in the brain.
Yet for almost a century, scientists believed that neuromodulators like norepinephrine adjusted brain communication by acting directly on neurons.
The study, conducted by researchers from Washington University in St. Louis, Missouri, showed that astrocytes, not neurons, drive attention, alertness, and numerous other functions.
Thomas Papouin and his colleagues stimulated norepinephrine secretion from mouse brain cells or exposed mouse brain slices to norepinephrine. They confirmed that, as known for decades, norepinephrine weakened connections between neurons.
But they noticed something critical: Norepinephrine also triggered activity among the astrocytes that surrounding the neurons.
They showed that when astrocytes detected norepinephrine, they produced a second chemical messenger, which dampened synaptic activity and directed neuron communication.
Now for the cool part.
If the neurons were prevented from sensing norepinephrine, the effect remained as long as astrocytes functioned.
But when astrocytes’ ability to sense or respond to norepinephrine was silenced, norepinephrine lost its influence on the connectivity between neurons.
The long-maligned star-shaped astrocyte cells, it turns out, are the active gatekeepers of brain function.
They control how entire neural networks switch on and off in response to neuromodulators like dopamine, norepinephrine, serotonin, and glutamate.
A single astrocyte can influence hundreds of neurons and thousands of synapses by releasing molecules known as gliotransmitters.
This makes them the stars of the neural show.
This discovery opens new therapeutic avenues for the treatment of attention and mood disorders traditionally addressed by drugs that target neurons—and that we know have less efficacy than we’d like.
Papouin’s team has started looking at existing drugs that are believed to act on neurons, to determine whether they require astrocytes to be effective. If this is the case, astrocytes could be targeted directly for therapeutic purposes.
Thomas Papouin, Ph.D., assistant professor of neuroscience at Washington University School of Medicine and the principal investigator of the study, spoke to Neuroscience News about the discovery. “So many drugs out there interfere with norepinephrine signaling in the brain, particularly in the treatment of ADHD or depression,” Papouin said. “I wonder how many of them require astrocytes to modify brain activity.”
To summarize the main implications of this study and others that preceded it:
Norepinephrine (and perhaps dopamine and serotonin) reorganizes brain activity not through neurons but through astrocytes.
Astrocytes release a secondary signal that weakens synaptic connections in response to norepinephrine.
Targeting these gatekeeper astrocytes may improve treatment of attention and mood disorders.
Science, the journal that published Papouin’s study, also published two companion papers on astrocytes, showing the cells’ influence on both dopamine and the ATP/adenosine pathway.
These studies are paradigm-shifting.
They point to the dynamics of a neural symphony, in which astrocytes and glial cells are the conductors that direct coherence and response on a global level. These cells regulate neural synchrony, entropy, and shifting states of attention. Rather than leveling neurotransmitters at neurons, medicine now has the potential to refine the way conductors relate to the musicians (the body and brain “instruments”) and to the way they play together and apart.
The Papouin study’s paper doesn’t mention this, but I’d seen astrocytes show up again and again in my research into Parkinson’s disease, as well as its role in neuro-inflammation.
Additional Implications of The Study
Our brains have connective tissue, which provides a support network for blood vessels and nerves. This connective tissue is comprised not only of neurons, but glial cells—and, specifically, astrocytes.
In the brain, astrocytes play a critical role in maintaining the blood-brain barrier, which keeps inflammatory molecules in the bloodstream from entering the brain.
Astrocytes also exist in the gut, where they are known as enteric glial cells, and are influenced by gut microbial balance.
In this article, I explored the links between the breakdown of enteric (gut-based) epithelial cells and a rise in levels of lipopolysaccharide (LPS), inflammatory molecules which cross first the gut-blood barrier and then the blood-brain barrier . Once in the brain, they play a causal role in the decades-long development of Parkinson’s disease.
Astrocytes can contribute to the clearance or transmission of α-synuclein, a protein that plays a significant role in the development of neurodegenerative disorders like Parkinson’s.
Astrocytes also factor in epilepsy, autism spectrum disorder, and neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and cerebellar ataxias.
These star-shaped cells also communicate with immune cells such as microglia, T cells, and natural killer cells through molecules secreted during neuroinflammation.
Astrocyte function is adversely affected by glucocorticoids from chronic stress, air pollution, toxic environmental substances like chemical fertilizers and plasticizers, gut microbe imbalances (and again, high circulating lipopolysaccharides or LPS), insufficient sunlight, and insufficient endogenous nighttime melatonin.
My background as a research assistant at the University of Chicago’s Sleep Research Lab gave me a lifelong obsession with the functions of sleep, which is intimately involved with astrocytes.
Astrocytes drive the brain’s glymphatic system, which removes toxic byproducts and waste from the brain. The glymphatic system reaches its peak of activity during slow-wave sleep, which we have more of during the first half of the night. (This means that all the things we do to maintain a consistent bedtime, to fall asleep before 11:00 p.m. to have the best portion of slow-wave sleep possible, to delay caffeine after awakening, and to reduce light exposure at night, all aid the functioning of the glymphatic system.)
And according to emerging research in neurobiology, astrocytes and other glia (and microglia) microglia affect the synthesis and functioning of other neuromodulators—think dopamine, endorphins, and oxytocin—that regulate neuroinflammation and social bonding. Astrocytes, researchers believe, may be system-level regulators of the neuromodulation of social behavior.
Astrocytes are also at the cutting edge of new drug delivery systems for brain diseases.
Final Reflections About The Study
In closing, let me situate this discovery in its current socio-political context.
First, the study focuses on brain health, which means that we want to position astrocyte-centered interventions alongside factors like exercise (and novel movement), women’s health (such as menopause), and the social determinants of health.
And there’s the sobering reality of research funding in the U.S. in 2025.
This study was funded by four grants from the National Institutes of Health (NIH), the U.S. Department of Defense, the Brain and Behavior Research Foundation, the Whitehall Foundation, and the McDonnell Center for Cellular and Molecular Neurobiology at Washington University.
This is just the sort of discovery that the U.S. administration’s funding cuts will impact.
In fact, in April of 2025, the Trump administration ended $1.8 billion in grants to the National Institutes of Health. This included $544 million in funds that have been promised but not yet spent.
According to NBC News, the administration terminated nearly 700 grants across 24 NIH institutes and centers focused on subjects such as aging, cancer, child health, diabetes, mental health and neurological disorders.
The cuts, it turns out, were not spread evenly. Michael Liu, a student at Harvard Medical School, examined the cuts in depth for a recent study.
“The National Institute on Minority Health and Health Disparities was hit the hardest,” Liu said. “About 30% of all of its funding was cut. That’s 10 times more than the average.”
President Donald Trump’s new budget proposal would eliminate all funding for the National Institute on Minority Health and Health Disparities next year, and refers to the institute as “replete with DEI expenditures.”
Sources:
A single human brain contains almost as many neurons: Are There Really as Many Neurons in the Human Brain as Stars in the Milky Way? | Brain Metrics | Learn Science at Scitable. (n.d.). Retrieved May 22, 2025, from https://www.nature.com/scitable/blog/brain-metrics/are_there_really_as_many/ Herculano-Houzel S. (2009). The human brain in numbers: a linearly scaled-up primate brain. Frontiers in human neuroscience, 3, 31. https://doi.org/10.3389/neuro.09.031.2009
Yet in many parts of the mammalian brain, neurons comprise only 10-20 percent: Kelly, D. A. (n.d.). Neurons and Glia: Basic Components of the Nervous System. Retrieved May 22, 2025, from https://www.brainfacts.org:443/brain-anatomy-and-function/cells-and-circuits/2022/neurons-and-glia-113022
Astrocytes communicate using multiple mechanisms, including the release of chemical: Hastings, N., Yu, Y.-L., Huang, B., Middya, S., Inaoka, M., Erkamp, N. A., Mason, R. J., Carnicer-Lombarte, A., Rahman, S., Knowles, T. P. J., Bance, M., Malliaras, G. G., & Kotter, M. R. N. (2023). Electrophysiological In Vitro Study of Long-Range Signal Transmission by Astrocytic Networks. Advanced Science, 10(29), 2301756. https://doi.org/10.1002/advs.202301756
Norepinephrine plays a vital part in regulating arousal, attention, working memory: Hussain, L. S., Reddy, V., & Maani, C. V. (2025). Physiology, Noradrenergic Synapse. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK540977/
And yet, nearly half of all people with depression have no clinical response to two or more: Saelens, J., Gramser, A., Watzal, V., Zarate, C. A., Lanzenberger, R., & Kraus, C. (2025). Relative effectiveness of antidepressant treatments in treatment-resistant depression: A systematic review and network meta-analysis of randomized controlled trials. Neuropsychopharmacology, 50(6), 913–919. https://doi.org/10.1038/s41386-024-02044-5 See also: Papadimitropoulou, K., Vossen, C., Karabis, A., Donatti, C., & Kubitz, N. (2017). Comparative efficacy and tolerability of pharmacological and somatic interventions in adult patients with treatment-resistant depression: a systematic review and network meta-analysis. Current medical research and opinion, 33(4), 701–711. https://doi.org/10.1080/03007995.2016.1277201
low-dose naltrexone (LDN), which can reduce inflammation in people with major depression: Plank, J. R., Glover, S. C., Moloney, B. D., Hoeh, N. R., Sundram, F., Sumner, R. L., Muthukumaraswamy, S., & Lin, J. C. (2022). A randomized, double-blind, placebo-controlled, hybrid parallel-arm study of low-dose naltrexone as an adjunctive anti-inflammatory treatment for major depressive disorder. Trials, 23(1), 822. https://doi.org/10.1186/s13063-022-06738-3
Importantly, considerable speculation remains as to whether clinical responses: Witt, C. E., Mena, S., Holmes, J., Hersey, M., Buchanan, A. M., Parke, B., Saylor, R., Honan, L. E., Berger, S. N., Lumbreras, S., Nijhout, F. H., Reed, M. C., Best, J., Fadel, J., Schloss, P., Lau, T., & Hashemi, P. (2023). Serotonin is a common thread linking different classes of antidepressants. Cell Chemical Biology, 30(12), 1557-1570.e6. https://doi.org/10.1016/j.chembiol.2023.10.009
Yet serotonin remains a key thread that weaves together: Witt, C. E., Mena, S., Holmes, J., Hersey, M., Buchanan, A. M., Parke, B., Saylor, R., Honan, L. E., Berger, S. N., Lumbreras, S., Nijhout, F. H., Reed, M. C., Best, J., Fadel, J., Schloss, P., Lau, T., & Hashemi, P. (2023). Serotonin is a common thread linking different classes of antidepressants. Cell Chemical Biology, 30(12), 1557-1570.e6. https://doi.org/10.1016/j.chembiol.2023.10.009
Thomas Papouin and his colleagues stimulated norepinephrine secretion from mouse: News, N. (2025, May 16). Astrocytes, Not Neurons, Drive Brain’s Attention and Alertness. Neuroscience News. https://neurosciencenews.com/astrocytes-alertness-attention-28939/
A single astrocyte, it turns out, can influence hundreds of: Source: Research Topics. (2018, September 19). Papouin Lab. https://sites.wustl.edu/papouinlab/research/
Thomas Papouin, Ph.D., assistant professor of neuroscience at Washington University: News, N. (2025, May 16). Astrocytes, Not Neurons, Drive Brain’s Attention and Alertness. Neuroscience News. https://neurosciencenews.com/astrocytes-alertness-attention-28939/
Science, the journal that published Papouin’s study, also published: Guttenplan, K. A., Maxwell, I., Santos, E., Borchardt, L. A., Manzo, E., Abalde-Atristain, L., Kim, R. D., & Freeman, M. R. (2025). GPCR signaling gates astrocyte responsiveness to neurotransmitters and control of neuronal activity. Science, 388(6748), 763–768. https://doi.org/10.1126/science.adq5729 See also: Chen, A. B., Duque, M., Rymbek, A., Dhanasekar, M., Wang, V. M., Mi, X., Tocquer, L., Narayan, S., Legorreta, E. M., Eddison, M., Yu, G., Wyart, C., Prober, D. A., Engert, F., & Ahrens, M. B. (2025). Norepinephrine changes behavioral state through astroglial purinergic signaling. Science, 388(6748), 769–775. https://doi.org/10.1126/science.adq5233
In the brain, astrocytes play a critical role in maintaining the blood-brain barrier: Wei, D. C., & Morrison, E. H. (2025). Histology, Astrocytes. In StatPearls. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/books/NBK545142/
Astrocytes also exist in the gut, where they are known as enteric: Zhao, Y. F., Wei, D. N., & Tang, Y. (2021). Gut Microbiota Regulate Astrocytic Functions in the Brain: Possible Therapeutic Consequences. Current neuropharmacology, 19(8), 1354–1366. https://doi.org/10.2174/1570159X19666210215123239
Astrocytes can contribute to the clearance or transmission of α-synuclein: Brash-Arias, D., García, L. I., Pérez-Estudillo, C. A., Rojas-Durán, F., Aranda-Abreu, G. E., Herrera-Covarrubias, D., & Chi-Castañeda, D. (2024). The Role of Astrocytes and Alpha-Synuclein in Parkinson’s Disease: A Review. NeuroSci, 5(1), Article 1. https://doi.org/10.3390/neurosci5010005
Astrocytes also play a key role in neurodegenerative disorders such as: Zhao, Y. F., Wei, D. N., & Tang, Y. (2021). Gut Microbiota Regulate Astrocytic Functions in the Brain: Possible Therapeutic Consequences. Current neuropharmacology, 19(8), 1354–1366. https://doi.org/10.2174/1570159X19666210215123239
And these star-shaped cells communicate with immune cells such as: Lee, S. Y., & Chung, W.-S. (2024). Astrocytic crosstalk with brain and immune cells in healthy and diseased conditions. Current Opinion in Neurobiology, 84, 102840. https://doi.org/10.1016/j.conb.2024.102840
Astrocyte function is adversely affected by glucocorticoids: Naour, A. L., Beziat, E., Kam, J. H., Magistretti, P., Benabid, A. L., & Mitrofanis, J. (2023). Do astrocytes respond to light, sound, or electrical stimulation?. Neural regeneration research, 18(11), 2343–2347. https://doi.org/10.4103/1673-5374.371343
And astrocytes drive the brain’s glymphatic system, which removes toxic: Ding, Z., Fan, X., Zhang, Y., Yao, M., Wang, G., Dong, Y., Liu, J., & Song, W. (2023). The glymphatic system: a new perspective on brain diseases. Frontiers in aging neuroscience, 15, 1179988. https://doi.org/10.3389/fnagi.2023.1179988
And according to emerging research in neurobiology, astrocytes and other glia (and microglia) microglia affect the synthesis: Loth, M. K., & Donaldson, Z. R. (2021). Oxytocin, Dopamine, and Opioid Interactions Underlying Pair Bonding: Highlighting a Potential Role for Microglia. Endocrinology, 162(2), bqaa223. https://doi.org/10.1210/endocr/bqaa223
This study was funded by four grants from the National Institutes of Health: Lefton, K. B., Wu, Y., Dai, Y., Okuda, T., Zhang, Y., Yen, A., Rurak, G. M., Walsh, S., Manno, R., Myagmar, B.-E., Dougherty, J. D., Samineni, V. K., Simpson, P. C., & Papouin, T. (2025). Norepinephrine signals through astrocytes to modulate synapses. Science, 388(6748), 776–783. https://doi.org/10.1126/science.adq5480
In fact, in April of 2025, the Trump administration ended $1.8 billion in grants: Trump administration cut more than $1.8 billion in NIH grants. (2025, May 8). NBC News. https://www.nbcnews.com/health/health-news/trump-administration-cut-18-billion-nih-grants-rcna205568
According to NBC News, the administration terminated nearly 700 grants across 24 NIH: https://www.nbcnews.com/health/health-news/trump-administration-cut-18-billion-nih-grants-rcna205568
Thank you for this!