The Aging Brain: It Starts Earlier Than You Think (5)

Beyond Neurons

In this post I will introduce a long-neglected element of brain aging, glial cells. Until quite recently, studies of brain aging have focused exclusively on neurons. But neurons comprise only half of the brain. The other half consists of cells collectively known as glia. Glia is Greek for glue, which was long thought to be the sole function of these cells. We now know that glial cells are essential for all brain processes, including cognition.

There are several kinds of glial cells. I will first consider the most common of these, called astrocytes (“astro” is Greek for star, “cyte” is Latin for cell). Astrocytes (star cells) are so called because of their projections that radiate in all directions from a central cell body. Astrocyte projections extend through every nanometer of brain space, through both gray matter and white matter and all blood vessels therein.

Astrocytes and Neural Plasticity

The capacity of neurons to form new connections with other neurons is called neuroplasticity, a hallmark of a healthy brain. The paradigmatic connection between neurons is a structure called the synapse. So, for our purposes, neuroplasticity is synonymous with synaptic plasticity. The creation of new synapses (synaptogenesis) is largely directed by astrocytes. Moreover, astrocytes are necessary for synapse maintenance. As if that weren’t enough, we now know that astrocytes projections are key structural components of the synapses themselves.

On the traditional view of synapses there are two components, a presynaptic neuron and a postsynaptic neuron. For most synapses, the presynaptic element and the post synaptic element are not physically connected. Rather, they are separated by a gap. Signal transmission across the gap is a chemical process. The chemicals that transmit the signal across the gap are called neurotransmitters.

Call the traditional view of synaptic signaling the bipartite (two part) synapse. We now know that most synapses are tripartite (10.1016/s0166-2236(98)01349-6). The third element is an astrocyte projection. The astrocyte element of the synapse does not produce neurotransmitters, but it does influence neuron-neuron signaling in several ways. Mounting evidence suggests than one of the ways in which astrocytes influence neuron-neuron signaling is through their release of chemicals called gliotransmitters, the glial analog of neurotransmitters. Gliotransmitters, modulate the effects of the neurotransmitters released at the synapse.

A single neuron may participate in hundreds to thousands of synapses. But a single astrocyte cell may modulate 100,000 synapses from hundreds of neurons. Moreover, these hyper connected astrocytes have a capacity that neurons don’t. As a result of astrocyte-to-astrocyte communication that is not fully understood, hundreds to thousands of astrocytes can respond to a stimulus simultaneously, as if they were a single cell. As a result, astrocytes can influence neural signaling on larger scales than neuronal interactions alone.

Without astrocytes, synapses wither. When synapses wither, neurons lose vigor. When neurons lose vigor, neural networks decay. Since loss of synapses, and the consequent loss of neuroplasticity is characteristic of the aging brain, astrocytes have received increasing attention in research on brain aging. There is mounting evidence that brain aging begins with astrocytes—and other glia—not the neurons themselves. For this reason, much recent research on brain aging concerns the causes of astrocyte senescence and how best to arrest it. That will be the topic of the next post in this series.