Microglia eat neural stem cells in developing rat and monkey brains

By Meghan Rosen

Web edition: March 5, 2013

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Over two hours, a rat embryonic microglial cell (green, marked with asterisk) engulfs a neighboring brain stem cell (red, marked with arrow). Once engulfed, the stem cell appears yellow. Researchers think that microglia gobble up neural stem cells to prune brain size during development.

Credit: Cunningham, et al. The Journal of Neuroscience 2013. Reprinted with permission.

Zombies aren’t the only things that feast on brains. Immune cells called microglia gorge on neural stem cells in developing rat and monkey brains, researchers report in the March 6 Journal of Neuroscience.

Chewing up neuron-spawning stem cells could help control brain size by pruning away excess growth. Scientists have previously linked abnormal human brain size to autism and schizophrenia.

“It shows microglia are very important in the developing brain,” says neuroscientist Joseph Mathew Antony of the University of Toronto, who was not involved in the research.

Scientists have long known that in adult brains, microglia hunt for injured cells as well as pathogens. “They mop up all the dead and dying cells,” Antony says.

And when the scavengers find a dangerous intruder, they pounce. “These guys are relentless,” says study coauthor Stephen Noctor, of the University of California, Davis MIND Institute in Sacramento. “They seek and destroy bacteria — it’s really quite amazing.”

Microglia also lurk in embryonic brains, but the immune cells’ role there is less well understood.

Previous studies had found microglia near neural stem cells — tiny factories that pump out new neurons. When Noctor’s team examined slices of embryonic human, monkey and rodent brains, he was struck by just how many microglia crowded around the stem cells and how closely the two cell types touched.

Given the cells’ cozy contact, he figured that the microglia and the neural stem cells must interact.

Noctor and colleagues injected embryonic rat brains with a compound to make their neural stem cells glow red. One day later, the team shaved the brains into thin slices, and kept the tissue alive in an incubator. Next, the researchers dyed the brain slices’ microglia green and snapped time-lapse microscopy images of the colored cells in action.

A series of these images unfolds like a scene from a brain-cell horror movie. First, a green-stained microglial cell sidles up to a pack of red-glowing stem cells. Then the immune cell singles out a stem cell and embraces it. Finally, the green cell swallows the red cell whole. After about two hours, all traces of the victim have vanished. A microglial cell’s touch, Noctor says, is “like the kiss of death.”

In a separate experiment, Noctor’s team looked at stained microglia and neural stem cells in thin slices of embryonic monkey brain. Here too, the team saw evidence of microglial feasts: The team captured images of green microglia with bits of digested red stem cells in their bellies.

Though a microglial cell isn’t much bigger than the cell it devours, the immune cell’s outer membrane can expand to accommodate its meal, says Noctor. It’s like a pair of elastic-waist pants making room for Thanksgiving dinner.

To find out the effect of this munching on the brain, Noctor’s team used chemicals that rev up or tamp down microglial appetites. Tinkering with the immune cells’ activity altered the number of rat neural stem cells, they found. When his team used a drug to wipe microglia from embryonic rat brains, the neural stem cells in these animals grew unchecked.

Noctor now plans to examine these rats’ brain architecture, to figure out whether removing microglia affects long-term neurodevelopment.

“The study is going to be a big help to the field,” says neuroscientist Gwenn Garden of the University of Washington in Seattle. The results clearly show that microglia target living neural stem cells, she says, although their role in developmental disorders is still unclear.