New neurons don’t heal

Study shows neurogenesis doesn’t produce all the cell types needed to repair brain injury

Rubbernecking neurons don’t do an injured brain any good. Newborn neurons rush to the scene of the damage but don’t pitch in to help heal the wound, a new study shows.

Scientists have had great hopes that new neurons produced in the brain after a stroke or other insult could migrate to the wounded area and replace damaged cells. Previous research has shown that the newborns are attracted to injury sites, but a new study that appears in the April 22 Journal of Neuroscience shows that those neurons don’t form replacements for the majority of cells. The results indicate that simply boosting neuron production may not help heal the brain.

Zhengang Yang of Fudan University in Shanghai and colleagues induced strokes in a part of rats’ brains called the striatum, which controls movement, and marked new neurons so the cells could be traced as they migrated through the brain. The researchers examined the cells for certain proteins that are hallmarks of different neuron types, to see which kind of neuron the cells differentiated into.

Previous research has shown that new neurons are born in the adult brain in two places — the hippocampus and the subventricular zone, or SVZ. Neurons born in the SVZ usually migrate to the olfactory bulb. But after a stroke, some of the new SVZ neurons flock to the wound site.

Yang and his colleagues show in the new study that the new SVZ neurons don’t form medium-sized spiny neurons, the type of cell most common in the striatum. Only neurons producing calretinin and Sp8, two markers of olfactory bulb neurons, migrate into the wounded striatum. There, the neurons form the same type that they would in the olfactory bulb, if they survive at all.

The result suggests that instead of being a rescue squad, the new neurons are mostly misdirected olfactory bulb neurons attracted to the injury site like rubberneckers to the scene of an accident.

More worrisome is that few survive and integrate into the striatum’s network, says Jack Parent, a neurologist and neuroscientist at the University of Michigan Medical School in Ann Arbor.

“It’s good that they are attracted to the injury,” Parent says. “That’s half the battle. The real key is getting them to hook up.”

It isn’t clear why the new study differs from earlier work that suggests newborn SVZ cells can produce multiple types of neurons, Parent says. What the scientists agree on is that the new neurons’ programming is important in determining future identity.

“This study tells us that the local environment is probably very important for telling stem cells what to do,” says Hongjun Song, a neuro–stem cell biologist at Johns Hopkins University in Baltimore. “They need help to change their fate.”

Yang isn’t giving up on the idea of using new neurons to repair brain injuries. He points to techniques to reprogram skin cells into embryonic-like stem cells as inspiration. “Somehow, in the future, we could use several different scientific methods together to coax adult neural stem cells into becoming various types of neurons,” he says.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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