Beyond neurons: How cells called astrocytes contribute to brain disorders: New research in mice pinpoints disease-modifying molecules produced by astrocytes in Rett, fragile X and Down syndromes

Neurons often get most of the credit for keeping our brains sharp and functioning — as 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.

As the team reports in Nature Neuroscience on August 30, 2022, blocking the molecule reduces the signs of disease in mice brains.

“These findings are part of a new push to look at how all the cells in the brain, not just neurons, interact in neurodevelopmental disorders,” says Associate Professor Nicola Allen, who led the new study. “This opens the door to potential therapeutics to treat these disorders by targeting astrocytes.”

In recent years, scientists have discovered that astrocytes play key roles in brain development and disease. Isolated neurons, for instance, don’t 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.

However, researchers haven’t been able to pin down what molecules from astrocytes are responsible.

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 — 88 at higher-than-usual levels, and 32 at lower-than-usual levels.

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