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. 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, 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 the senior author of 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, the researchers 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.
“From a basic science perspective, it’s fascinating that there are so many changes seen in astrocyte protein secretion in these genetic disorders—and more importantly, that so many of those changes overlap between the disorders,” says the first author of the paper. “To me, this highlights how important astrocytes are for normal neuronal development.”
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’t producing enough IGF. But they found a different explanation—astrocytes impacted by Rett, fragile X or Down syndrome make high levels of Igfbp2, a protein that blocks IGF.
“It turns out that neurons are making plenty of IGF, but it can’t get where it needs to be because these molecules made by astrocytes are interfering with it,” says the senior author.
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.
“We still have a long way to go to get a therapy based on this to humans, but we think it has promise,” says the author. “Rather 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.”
https://www.nature.com/articles/s41593-022-01150-1
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Faberrant-astrocyte&filter=22&redirected=1
How astrocytes contribute to brain developmental disorders
- 946 views
- Added
Latest News
Father's gut microbes affec…
By newseditor
Posted 08 May
A new brain circuit in mice…
By newseditor
Posted 08 May
Mechanism of choline entry…
By newseditor
Posted 07 May
Link between UTI and breast…
By newseditor
Posted 07 May
Sleep resets brain connections
By newseditor
Posted 07 May
Other Top Stories
How neural circuits drive hungry individuals to peak performance
Read more
Nuclear war between India and Pakistan could kill millions worldwide
Read more
Multi-generational effect on immune system by environmental toxins
Read more
Aspirin cuts the toxic effects of air pollution on lungs
Read more
DNA methylation test to measure developmental age of children in he…
Read more
Protocols
Single-cell adhesive profil…
By newseditor
Posted 07 May
Parasympathetic neurons der…
By newseditor
Posted 07 May
Non-invasive measurements o…
By newseditor
Posted 05 May
A validation strategy to as…
By newseditor
Posted 04 May
Generation of rat forebrain…
By newseditor
Posted 03 May
Publications
Paternal microbiome perturb…
By newseditor
Posted 08 May
Truncating NFKB1 variants c…
By newseditor
Posted 08 May
Synaptotagmin-11 facilitate…
By newseditor
Posted 08 May
Astrocytic Slc4a4 regulates…
By newseditor
Posted 08 May
Diabetic retinopathy is a c…
By newseditor
Posted 08 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar