Astrocytes Have an Unexpected Role in Brain Plasticity

Summary: A new study reports a protein made by astrocytes plays a critical role in brain plasticity by assisting with neural maturation and flexibility.

Source: Salk Institute.

When we’re born, our brains have a great deal of flexibility. Having this flexibility to grow and change gives the immature brain the ability to adapt to new experiences and organize its interconnecting web of neural circuits. As we age, this quality, called “plasticity,” lessens.

In a study published October 18, 2018 in Neuron, a team from the Salk Institute has shown that astrocytes–long-overlooked supportive cells in the brain–help to enable the brain’s plasticity, a new role for astrocytes that was not previously known. The findings could point to ways to restore connections that have been lost due to aging or trauma.

“We knew from our previous work that astrocytes are important for the development of the brain; however, we knew very little about the role of astrocytes in the adult brain,” says Nicola Allen, assistant professor and the study’s senior author. “To investigate this role, we used a lot of techniques in the lab to identify a signal made by astrocytes that’s very important for brain maturation.”

The signal turned out to be a protein astrocytes secrete called Chrdl1, which increases the number and maturity of connections between nerve cells, enabling the stabilization of neural connections and circuits once they finish developing.

To further understand the role of Chrdl1, the team developed mouse models with the gene disabled by introduced mutations. These mice had a level of plasticity in their brains that was much higher than normal. Adult mice with the Chrdl1 mutation had brain plasticity that looked very much like that of young mice, whose brains are still in early stages of development.

“It’s important to study brain plasticity, because it teaches us how the brain remodels itself in response to new experiences,” says first author Elena Blanco-Suarez, a research associate in Allen’s lab. “Although some degree of plasticity is important, it decreases as we become older. Nature has designed these circuits to become more stable and less flexible. Otherwise, our brains would not mature and we would experience our whole life like a young child does.”

Not much is known about the role of Chrdl1 in humans, but one study of a family with a Chrdl1 mutation showed they performed extremely well in memory tests. Other studies have shown the level of the gene encoding Chrdl1 is altered in schizophrenia and bipolar disorder, suggesting that Chrdl1 may have important roles in both health and disease.

astrocytes
Astrocytes are the main cell type in the brain producing Chrdl1. Through a technique called fluorescence in situ hybridization, the RNA of different proteins is tagged with fluorescent labels. In the image, Chrdl1 is in red, astrocytes in cyan (teal) and neurons in dark blue, in the upper layers of the mouse visual cortex. The signal from Chrdl1 overlaps with astrocytes, but not with neurons, indicating that astrocytes are the cells that mainly produce Chrdl1. NeuroscienceNews.com image is credited to Salk Institute.

Future research by the team will dive deeper into the relationships between astrocytes and neurons and look for potential ways to use astrocytes as therapy.

“We’re interested in learning more about what the astrocytes are secreting into the brain environment and how those signals affect the brain,” says Allen. “We plan to look at this relationship both early in development and in situations where those connections are lost and you want to stimulate repair, like after someone has had a stroke.”

About this neuroscience research article

Other researchers on the paper were Tong-Fei Liu and Alex Kopelevich of Salk.

Funding: This work was funded by National Institutes of Health grant NS105742, the Hearst Foundation, the Pew Charitable Trusts, the Lawrence Ellison Foundation, the Whitehall Foundation, the Helmsley Foundation and the Catarina Foundation.

Source: Salk Institute
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Salk Institute.
Original Research: Abstract for “Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits Plasticity by Increasing Synaptic GluA2 AMPA Receptors” by Elena Blanco-Suarez, Tong-Fei Liu, Alex Kopelevich, and Nicola J. Allen in Neuron. Published October 18 2018.
doi:10.1016/j.neuron.2018.09.043

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Salk Institute”Astrocytes Have an Unexpected Role in Brain Plasticity.” NeuroscienceNews. NeuroscienceNews, 18 October 2018.
<https://neurosciencenews.com/astrocytes-plasticity-10045/>.[/cbtab][cbtab title=”APA”]Salk Institute(2018, October 18). Astrocytes Have an Unexpected Role in Brain Plasticity. NeuroscienceNews. Retrieved October 18, 2018 from https://neurosciencenews.com/astrocytes-plasticity-10045/[/cbtab][cbtab title=”Chicago”]Salk Institute”Astrocytes Have an Unexpected Role in Brain Plasticity.” https://neurosciencenews.com/astrocytes-plasticity-10045/ (accessed October 18, 2018).[/cbtab][/cbtabs]


Abstract

Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits Plasticity by Increasing Synaptic GluA2 AMPA Receptors

In the developing brain, immature synapses contain calcium-permeable AMPA glutamate receptors (AMPARs) that are subsequently replaced with GluA2-containing calcium-impermeable AMPARs as synapses stabilize and mature. Here, we show that this essential switch in AMPARs and neuronal synapse maturation is regulated by astrocytes. Using biochemical fractionation of astrocyte-secreted proteins and mass spectrometry, we identified that astrocyte-secreted chordin-like 1 (Chrdl1) is necessary and sufficient to induce mature GluA2-containing synapses to form. This function of Chrdl1 is independent of its role as an antagonist of bone morphogenetic proteins (BMPs). Chrdl1 expression is restricted to cortical astrocytes in vivo, peaking at the time of the AMPAR switch. Chrdl1 knockout (KO) mice display reduced synaptic GluA2 AMPARs, altered kinetics of synaptic events, and enhanced remodeling in an in vivo plasticity assay. Studies have shown that humans with mutations in Chrdl1 display enhanced learning. Thus astrocytes, via the release of Chrdl1, promote GluA2-dependent synapse maturation and thereby limit synaptic plasticity.

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  1. I was wondering if or how this article reg. Astrocytes may relate to the type of brain tumor I have: Hypothalamus-Astrocytoma. I have 20% of the malignant tumor that is inoperable. However, with the 80%, they also had to sever my pituitary gland. My tumor has been stable for over 20 years, which is good because they gave me 3 years to live way back then. I’ve also been declared legally blind as a result of the 2nd of 5 procedures.
    So in short, the tumor hasn’t been an issue, the aneurism devloped as a result hasnt been bothersome either (unless you mind 2 diff types of possible time bombs hanging out in your head…lol). I just know that the human body was not designed to thrive, or even survive for that matter, without a functioning pituitary. I take about 30 pills a day in order to try and ‘replace’ what my body would have been doing on its own and needless to say, I am truly Blessed, its very difficult and at times feels inadequate. Like I’m missing that
    Schanasaequa (please excuse my spelling or lack there of).
    Any insight or advice or just information would be greatly appreciated. Also if you have any questions for me, please feel free to reach out, theres lots to study here…lol
    On a side note I was in a study in Ohio at a VA Hospital that mapped out my eye nastagnes (spelling). It was very in depth and gave the chance for about a dozen ‘white coats’ to get a very up close look at my situation… The equipment they used looked like something from NASA and people were on chairs, with magnifying glasses to get a good look at my eyes ‘in action’. The test results were impressive to a civillian like me, but the chart produced was spot on and remarkable to me as well. It was able to graph what each one of my eyes did independantly from eachother at the same time! One eye would circle and the other tremble or shake, even visibly to the naked eye. From my perspective, looking out, when they both get going, everything is double and teeters at an angle. And p.s. no periphial vision either, its 100% blind.
    In closing, I hope my situation could teach or help someone, even if its me being the one learning. Thank you for your time. Have a Blessed Day!
    Sincerely,
    J.D.

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