{"id":35818,"date":"2022-08-30T00:00:22","date_gmt":"2022-08-30T07:00:22","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=35818"},"modified":"2024-01-30T14:21:29","modified_gmt":"2024-01-30T22:21:29","slug":"beyond-neurons-how-cells-called-astrocytes-contribute-to-brain-disorders","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/zh\/news-release\/beyond-neurons-how-cells-called-astrocytes-contribute-to-brain-disorders\/","title":{"rendered":"Beyond neurons: How cells called astrocytes contribute to brain disorders"},"content":{"rendered":"

LA JOLLA\u2014Neurons often get most of the credit for keeping our brains sharp and functioning\u2014as well as most of the blame when it comes to brain diseases. But star-shaped cells called astrocytes, another abundant cell in the human brain, may bear the brunt of the responsibility for exacerbating the symptoms of some neurodevelopmental disorders. Salk Institute scientists have now identified a molecule produced by astrocytes that interferes with normal neuron development in Rett, fragile X and Down syndromes.<\/p>\n

\"Salk
Salk researchers studied the molecules produced by astrocytes, like those pictured, to understand how the cells play a role in neurodevelopmental disorders.
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\n

As the team reports in Nature Neuroscience<\/em><\/a> on August 30, 2022, blocking the molecule reduces the signs of disease in mice brains.<\/p>\n

\u201cThese findings are part of a new push to look at how all the cells in the brain, not just neurons, interact in neurodevelopmental disorders,\u201d says Associate Professor\u00a0Nicola Allen<\/a>, who led the new study. \u201cThis opens the door to potential therapeutics to treat these disorders by targeting astrocytes.\u201d<\/p>\n

In recent years, scientists have discovered that astrocytes play key roles in brain development and disease. Isolated neurons, for instance, don\u2019t form connections and communicate unless astrocytes are present. If astrocytes affected by disease are mixed with healthy neurons, the neurons begin showing signs of disease. Similarly, if neurons affected by neurodevelopmental disorders are exposed to healthy astrocytes, their function improves.<\/p>\n

However, researchers haven\u2019t been able to pin down what molecules from astrocytes are responsible.<\/p>\n

In the new study, Allen and colleagues isolated astrocytes and neurons from the developing brains of mice with genetic mutations causing Rett, fragile X or Down syndrome or from healthy animals. Then they determined the levels of 1,235 different proteins produced by each set of astrocytes. They found hundreds of proteins present at higher or lower levels in each disease, with 120 proteins in common between all three diseases\u201488 at higher-than-usual levels, and 32 at lower-than-usual levels.<\/p>\n

\"From
From left: Nicola Allen and Alison Caldwell
Click here<\/a> for a high-resolution image.
Credit: Salk Institute<\/figcaption><\/figure>\n

\u201cFrom a basic science perspective, it\u2019s fascinating that there are so many changes seen in astrocyte protein secretion in these genetic disorders\u2014and more importantly, that so many of those changes overlap between the disorders,\u201d says Alison Caldwell, first author of the paper and a former graduate student in Allen\u2019s lab. \u201cTo me, this highlights how important astrocytes are for normal neuronal development.\u201d<\/p>\n

One molecule stood out to the scientists. They knew that insulin-like growth factor (IGF) could sometimes reduce symptoms of disease in mice with neurodevelopmental disorders. Researchers had long assumed the treatment worked because diseased neurons weren\u2019t producing enough IGF. But they found a different explanation\u2014astrocytes impacted by Rett, fragile X or Down syndrome make high levels of Igfbp2, a protein that blocks IGF.<\/p>\n

\u201cIt turns out that neurons are making plenty of IGF, but it can\u2019t get where it needs to be because these molecules made by astrocytes are interfering with it,\u201d says Allen.<\/p>\n

The group went on to show that excess Igfbp2 produced by astrocytes is responsible for slowing the growth of neurons and that blocking Igfbp2 made by Rett syndrome astrocytes enhanced neuron growth. Moreover, when mice with Rett syndrome were treated with antibodies blocking Igfbp2, signs of disease in the brain were lessened.<\/p>\n

\u201cWe still have a long way to go to get a therapy based on this to humans, but we think it has promise,\u201d says Allen. \u201cRather than giving an IGF treatment that has actions throughout the whole body, it makes sense to target Igfbp2 in the brain, where we want IGF to act.\u201d<\/p>\n

Allen\u2019s lab group is planning follow-up studies on other proteins they identified in diseased astrocytes, as well as future experiments to better understand Igfbp2.<\/p>\n

Other authors included Laura Sancho, James Deng, Alexandra Bosworth, Audrey Miglietta, Jolene Diedrich and Maxim Shokhirev of Salk.<\/p>\n

The work was supported in part by Autism Speaks (Dennis Weatherstone Predoctoral Fellowship), the Chapman Foundation, the National Institute of Child Health and Human Development (F30HD106699), the Chan Zuckerberg Initiative, the Hearst Foundation and the Pew Foundation.<\/p>","protected":false},"featured_media":35894,"template":"","faculty":[81],"disease-research":[169,459,124],"class_list":["post-35818","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-nicola-allen","disease-research-autism","disease-research-glial-biology","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"\nBeyond neurons: How cells called astrocytes contribute to brain disorders - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/zh\/news-release\/beyond-neurons-how-cells-called-astrocytes-contribute-to-brain-disorders\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Beyond neurons: How cells called astrocytes contribute to brain disorders - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014Neurons often get most of the credit for keeping our brains sharp and functioning\u2014as well as most of the blame when it comes to brain diseases. 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