Unsung Astrocytes and the Plastic Brain
Research is moving forward, finding new avenues for stopping neurodegeneration.
Posted Nov 21, 2018
You can usually hear the term “brain cell” to refer to neurons, as if they are the only cell type present in the brain. They are not. Neurons can be considered the main cellular unit in our nervous system, as they are the ones that transfer the information by means of electrical and chemical signals.
But much of our brain cell content is actually made up of “glia.” This term includes oligodendrocytes, microglia, and astrocytes, which are found in the brain, plus other cells that make up the blood vessels that run through the brain. “Glia” is a word derived from Greek that means “glue,” as this mass of non-neuronal cells was once thought to have the sole function of keeping everything together.
However, the cells that are part of glia are quite diverse, and they have more than structural “gluing” and supportive functions.
Astrocytes: the Underrated Stars
Astrocytes are the most abundant glial cell type. Their name, also from Greek, means “star cell.” They provide nutrients and physical support to neurons, and they are also in charge of maintaining the delicate chemical balance in the brain. Astrocytes have received quite some attention as they make up the so-called glial scar.
In more recent years, researchers realized that astrocytes were doing more than just keeping the brain neat and building scars. In fact, they found that astrocytes have a very active role in helping neurons to create and develop their connections, called synapses. Astrocytes make and secrete a bunch of proteins (or factors) that are sent to neurons, like instructions, to promote the structural formation of synapses.
However, those synapses are “silent”: They can’t really communicate due to lack of certain receptors. The postsynaptic neuron (the receiver) needs receptors to catch those signals (neurotransmitters) coming from the presynaptic neuron (the sender).
Synapses go through different stages of development, maturation and stabilization, and it was previously unclear whether astrocytes had roles further than structural formation of synapses.
When synapses are immature, they have the ability to adapt and build brain circuits based on the experiences that the brain is exposed to. This ability is called plasticity. The older we get, the less plasticity the brain shows. Brain circuits show high plasticity at specific time windows during development, called critical periods. This is partially the reason for why learning a language, for example, seems harder at an older age.
As we get older, the synapses mature, and this maturation comes by replacement of some receptors by slightly different ones.
Recent research with mice, published by our lab last month, shows that astrocytes are responsible for that switch. This proves that astrocytes’ role goes beyond what was believed to be their functions of house-keeping and mere structural support, and they can regulate synaptic maturation.
Astrocytes’ Job is a Lifelong Endeavor
The astrocytic role in synaptic maturation suggested that they would also have a say in the brain’s plasticity, since the more mature the neurons are, the less plasticity is displayed.
Our circuits can’t stay immature for our entire lives. But might there be a way of making the adult brain as plastic as a 5-year-old's at a precise moment? For instance, after a stroke, the brain retains an incredible ability to repair its own damaged circuits, but the outcome is not always so favorable at older ages due to declining plasticity.
Could we then summon the power of astrocytes to promote plasticity? Could we fool our own brain to make it as plastic as it needs to be to rebuild broken circuits?
We saw that the effect of astrocytes on brain plasticity was not restricted to critical periods, but also appeared in adulthood, when the circuits are allegedly stable. The manipulation of astrocyte-secreted factors holds promise for boosting the brain’s ability to repair itself in the event of a stroke, a traumatic brain injury, or any other disorder that may depend on plasticity.
Why don’t astrocytes naturally come to the rescue? Because when we get older, our astrocytes also suffer. In fact, due to changes that come with age, astrocytes turn from friends to foes. For example, they start eliminating synapses and they decrease their production of cholesterol, which is necessary for brain health.
Unraveling the mechanisms by which astrocyte-secreted factors can form, develop, and mature synapses will shed light on why later in life, they become lazy in their outstanding mission. Knowing this could help figure out how to harness the power of astrocytes to regulate plasticity and use it for the benefit of the aging brain.
Elena Blanco-Suarez, Tong-Fei Liu, Alex Kopelevich, Nicola J. Allen. Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits Plasticity by Increasing Synaptic GluA2 AMPA Receptors, Neuron, 2018, ISSN 0896-6273, https://doi.org/10.1016/j.neuron.2018.09.043.