Photograph by Kettenmann et al., Neuron 2013
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Spidery microglia, in red.
Photograph by Kettenmann et al., Neuron 2013

Best Cells Ever

As a journalist I’m supposed to be impartial, I know. But today I’ll confess, I don’t love every cell the same. I have a very favorite kind, the microglia.

Microglia are immune cells that live in the brain. They’re multi-taskers and largely mysterious, which you can tell by the gamut of metaphors scientists use to describe them. Microglia are like soldiers and policemen, chameleons and spiders, housekeepers, gardeners, electricians, and
garbage collectors. Microglia can be active or resting, branched or blobby, harmful or protective. Are you in love yet?

I’ve had the pleasure of writing a few stories about microglia; the latest, about their possible role in autism, came out yesterday. But I’m not the only one falling for them. This week two elite journals published reviews about microglia. In Neuron there’s Microglia: New Roles for the Synaptic Stripper; and in Science, Microglia: Scapegoat, Saboteur, or Something Else?

So it seems like a good time to promote my pet cells. Here, for your thoughtful consideration, are the top five reasons to get interested in microglia.

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Hungry microglia after brain injury.

5. When something goes wrong, they’re first on the scene.

For decades, researchers only studied the immune role of microglia. They’re great soldiers. As soon as they spot trouble — invading bacteria, say, or a pile of protein trash — they rapidly transform from their delicate, tree-shaped resting state into a fat, mean blob, and eat up the problem. (Yes, they have bellies.)

4. They’re everywhere and always moving.

The brain has thousands of different types of cells, but a full 10 percent are microglia. Researchers used to think microglia were quiet and passive most of the time, hence the term ‘resting state’. But that changed in 2005, when Axel Nimmerjahn made movies of microglia in live, healthy brains. Turns out their spindly branches are constantly reaching out to the cells around them. “They’re very dynamic, much more than any other cell in the adult brain,” Nimmerjahn told me for a piece I wrote last year for Nature.

3. Sometimes their good intentions turn bad.

The new Science review tells a fascinating story about microglia and prion disease, the deadly brain disorder caused by misfolded proteins that quickly accumulate and spread from one neuron to another, killing them. Acting as soldiers, microglia do their best to engulf the culprits: Postmortem brain tissue of people who died from prion disease is chock-full of microglia. The cells can’t fight fast enough, though, and their presence seems to eventually make things worse. “Failure to degrade prions may transform microglia into well-meaning yet lethal saboteurs,” the review says. Because microglia are such fast and efficient patrollers, in other words, they may inadvertently facilitate the spread of the prions.

2. Microglia are important at the beginning of life, and the end.

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A microglial cell (green), with pieces of synapse (faint red) in its belly. From Dorothy Schafer

The most recent excitement in the world of microglia has nothing to do with disease. As Beth Stevens and Dori Schafer reported last year, microglia are crucial for pruning synapses, the connections between neurons, during early brain development. Just as microglia gobble up invading pathogens, they can engulf synapses that don’t get used, a key part of the learning process.

The new Neuron review points out something I didn’t know: Microglia also may be partly to blame for the cognitive decline that often happens in old age. Microglia get larger with age and lose some of their branches. The ones that remain tend to move slowly. All this could mean that old cells can’t fully fend off disease or trigger the synaptic changes needed for learning and memory.

1. Everything’s up for grabs.

Neurons, the most famous brain cells, have been actively studied for more than a century. There’s still a whole lot that’s mysterious about neurons, but still, scientists know the basics of how they fire, what chemicals they respond to, what genes they express. Microglia, in contrast, are only beginning to get some real attention. That means the field is ripe for discovery, and we’re likely to see a deluge of exciting microglia papers in the years and decades to come.