Gift-giving brain cells are lifeline to injured nerve cells

Astrocytes share energy-making mitochondria with neural neighbors

astrocytes

GIFT GIVER  Star-shaped astrocytes (green) may donate mitochondria to nerve cells in distress, helping the brain escape damage from stroke and possibly other maladies, a new study suggests. 

Lka/Wikimedia Commons (CC BY-SA 3.0)

Under duress, nerve cells get a little help from their friends. Brain cells called astrocytes send their own energy-producing mitochondria to struggling nerve cells. Those gifts may help the neurons rebound after injuries such as strokes, scientists propose in the July 28 Nature.

It was known that astrocytes — star-shaped glial cells that, among other jobs, support neurons — take in and dispose of neurons’ discarded mitochondria. Now it turns out that mitochondria can move the other way, too. This astrocyte-to-neuron transfer is surprising, says neuroscientist Jarek Aronowski of the University of Texas Health Science Center at Houston. “Bottom line: It’s sort of shocking.”

Study coauthor Eng Lo of Massachusetts General Hospital and Harvard Medical School cautions that the work is at a very early stage. But he hopes that a deeper understanding of this process might ultimately point out new ways to protect the brain from damage.  

Mitochondria produce the energy that powers cells in the body. Scientists have spotted the organelles moving into damaged cells in other parts of the body, including the lungs, heart and liver. The new study turns up signs of this mitochondrial generosity in the brain.

POWERED UP Mitochondria from astrocytes (red) make their way into a nerve cell’s main body (box 1) and its message-sending axon (box 2). Some astrocyte-made mitochondria seem to fuse with the neuron’s own mitochondria (yellow, box 3). K. Hayakawa et al/Nature 2016
Astrocytes produce mitochondria and shunt them out into the soup that surrounds cells, Lo and colleagues found. The researchers then put neurons into this mitochondria-rich broth. When starved of glucose and oxygen — a situation that approximates a stroke — the neurons took in the astrocyte-made organelles.

Not only did the mitochondria make it into neurons, they actually helped, though the researchers don’t yet understand how. Neurons with donated mitochondria better survived their starvation diet. When grown in dishes without extra mitochondria floating around, neurons were less able to weather the poor conditions, the researchers found.

Further experiments suggest that the transfer happens not just in lab dishes, but in the brains of mice. A day after mice received a strokelike injury, astrocyte-produced mitochondria showed up inside their neurons. The gift giving seems to depend on a protein called CD38, which sits on the outside of astrocytes and may detect distress signals. When CD38 wasn’t functioning, the mice had fewer mitochondria in their neurons. What’s more, the mice were worse at balancing on wires than mice with normal CD38 behavior, a deficit that may be linked to having too few mitochondria in neurons.

The results bolster the idea that mitochondria donations between cells may have tremendous therapeutic potential, says cardiac surgical researcher James McCully of Boston Children’s Hospital. He and colleagues have recently developed a technique to purify and inject mitochondria into infants with heart damage. So far, four infants have been treated, and two were able to go home from the hospital, McCully says.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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