Mental disorders promoted by astrocytes

Neurons usually get most of the credit for keeping our brains working well, as well as most of the blame when the brain malfunctions. However, star-shaped cells called astrocytes, another abundant cell class in the human brain, may be primarily responsible for the symptoms of some neurodevelopmental disorders. A recent study provides evidence of this and reveals the mechanisms that allow it.

In recent years, various investigations have ended up discovering that astrocytes play a fundamental role in brain development and in brain diseases. Isolated neurons, for example, do not form connections or communicate unless astrocytes are present. If disease-affected astrocytes mix with healthy neurons, they begin to show signs of disease. Similarly, if neurons affected by neurodevelopmental disorders are exposed to healthy astrocytes, their function improves.

However, the researchers have not been able to pinpoint which substances in the astrocytes are responsible.

In the new study, the team of Alison Caldwell and Nicola Allen, from the Salk Institute in the United States, isolated astrocytes and neurons from the developing brains of mice with genetic mutations that cause Rett syndrome, Down syndrome and fragile X syndrome. , and astrocytes and neurons from healthy animals. They then determined the levels of 1,235 different proteins produced by each set of astrocytes. For each disease, they found hundreds of proteins present at higher or lower levels than normal. Of these, 120 proteins were common in the three diseases: 88 with higher than normal levels and 32 with lower than normal levels.

“From a basic science standpoint, it’s fascinating that so many changes in astrocyte protein secretion are seen in these genetic disorders and, more importantly, that many of those changes appear in more than one of those genetic disorders.” disorders,” Caldwell notes. “To me, this highlights the importance of astrocytes for normal neuronal development.”

Astrocytes. (Image: Salk Institute)

One substance stood out to scientists. They knew that insulin-like growth factor, which is very similar to insulin, can sometimes reduce disease symptoms in mice with neurodevelopmental disorders. It had long been assumed that the treatment worked because the diseased neurons did not produce enough insulin-like growth factor. But the authors of the new study found that what is actually happening is that astrocytes affected by Rett, Fragile X or Down syndrome produce high levels of Igfbp2, a protein that blocks insulin-like growth factor.

In other words, neurons make a lot of insulin-like growth factor, but it can’t reach its destination because that substance made by astrocytes interferes with it.

“We still have a long way to go to prepare a therapy based on this that is applicable to humans, but we believe the prospects are good,” Allen argues. “Instead of giving insulin-like growth factor treatment that works throughout the body, it makes more sense to target Igfbp2 in the brain, where we want insulin-like growth factor to be able to do its job.”

Caldwell and Allen’s team presents the technical details of their discovery in the academic journal Nature Neuroscience, under the title “Aberrant astrocyte protein secretion contributes to altered neuronal development in multiple models of neurodevelopmental disorders.” (Font: NCYT by Amazings)