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Stanford University School of Medicine

Jekyll & Hyde tale unfolding within the human brain may explain neurodegenerative disease

Jekyll and HydeJudging from the very terms used to designate brain research -- neuroscience, neurology, neurobiology -- you might figure nerve cells (or neurons, as brain scientists like to call them) are the only cells in the brain worth knowing about or, indeed, the only cells resident in that organ.

Not true. In fact, neurons account for a measly 10 percent of the cells in a healthy human brain. And over the past 25 years Stanford brain scientist Ben Barres, MD, PhD, has arguably done as much as any human on earth to advance the status of the 90 percent of cells in the brain that aren't neurons. Among those are a particularly interesting group called astrocytes because of their star-shaped appearance, and they were the focus of a just-published study by Barres' group.

As I describe in a news release on the Nature paper:

While most of us haven't heard of astrocytes, these cells are four times as plentiful in the human brain as nerve cells. Once thought of as mere packing peanuts whose job it was to keep neurons from jiggling when we jog, astrocytes are now understood to provide critical hands-on support and guidance to neurons, enhancing their survival and shaping the shared connections between them that define the brain's labyrinthine circuitry.

It's also known that traumatic brain injury, stroke, infection and disease can transform these usually benign "resting astrocytes" into so-called "reactive astrocytes" with altered features and behaviors. But until recently, whether reactive astrocytes were up to good or evil was an open question.

It turns out they can go either way:

In 2012, Barres and his colleagues... identified two distinct types of reactive astrocytes, which they called A1 and A2. [Under some conditions] resting astrocytes somehow wind up getting transformed into A1s, which are primed to produce large volumes of pro-inflammatory substances. A2s... are induced by [other conditions and] produce substances supporting neuron growth, health and survival ....

In the new study, Barres and his colleagues delved deeper into this dichotomy, learned exactly what makes astrocytes morph into Mr. Hyde instead of Dr. Jekyll, proved that the latter are neurocidal maniacs and, provocatively, found A1s lurking in the vicinity of practically every nasty neurodegenerative disease you can name. More from the release:

[They] analyzed samples of human brain tissue from patients with Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and multiple sclerosis. In every case, they observed large numbers of A1s preferentially clustering where the disease was most active... [T]hese findings strongly imply that A1 formation is helping to drive neurodegeneration in these diseases.

"This is the most important discovery my lab has ever made," Barres told me. His team is in hot pursuit of the identity of the neuron-slaying toxin A1s almost certainly secrete, and of ways of blocking those bad astrocytes from forming in the first place.

Previously: Alzheimer's puzzle pieces are coming together, More than just glue, glial cells challenge neurons' top slot, Star-shaped cells nab new starring role in sculpting brain circuits and Neuroinflammation, microglia, and brain health in the balance
Photo by Carlos Varela

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