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Originally published Thursday, March 7, 2013 at 9:19 PM

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Researchers find chemical secret to recapturing youthful brain

The new research, says the study’s senior author, Dr. Stephen Strittmatter, helps point the way to therapies that might allow victims of stroke or spinal cord damage to “set back their brain’s clock” to a stage of development that would foster the rapid relearning of lost ski

Los Angeles Times

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WASHINGTON — Adults (especially parents) often find fault with the teenage brain. But they should admit that it is a powerful learning machine — and that sometimes, the grown-ups wish they could recapture its nimbleness.

New research, conducted by researchers at Yale University and published Wednesday in the journal Neuron, homes in on the genetic and chemical mechanics that could make that possible.

The new research, says the study’s senior author, Dr. Stephen Strittmatter, helps point the way to therapies that might allow victims of stroke or spinal-cord damage to “set back their brain’s clock” to a stage of development that would foster the rapid relearning of lost skills.

The present research was done in mice, but clinical trials in the planning stages could allow researchers to test on human adults agents that mimic the cognitive fountain of youth.

“It’s about going from adulthood back to adolescence, and in general that’s something we would not want to do,” said Strittmatter, a neurologist who directs Yale School of Medicine’s program on neuroscience, neurodegeneration and repair. “But in some cases, it could prove very helpful.”

In response to the world around it, the adolescent brain is a marvel of regeneration, wiring and rewiring itself constantly as its owner learns and refines the motor, social and perceptual skills that will form the foundation of his or her adult behavior. That ability to adapt, respond and repair on a dime is called plasticity.

The adult brain, says Strittmatter, “becomes cemented in place.” Compared with the highly plastic adolescent brain, it is hard-wired.

The Yale team focused on a gene that programs for the production of a central nervous system protein called Nogo Receptor 1. Earlier research had established that Nogo Receptor 1 stimulates the growth of connections between neurons, and that when it is plentiful in the brain, mice do not recover as well from brain and spinal cord injuries.

But the Yale researchers essentially took time-gap photographs of groups of brain cells and the way they connected to one another in the brains of mice. When they bred mice without the gene, they documented that even into adulthood, the cells they recorded continuously arranged themselves into constantly changing configurations themselves, at the same frantic pace seen in adolescent mice.

The brains of mice with normal levels of Nogo Receptor 1, by contrast, settled down to a more stately pattern of reconstitution.

Then, the Yale team tried something more audacious: When they chemically plugged up the Nogo receptors in the brains of adult mice, they found that even mice whose brains had made the transition to plodding adulthood regained the speed of an adolescent brain at wiring and rewiring itself.

Adult mice with normal levels of Nogo Receptor 1 needed to live in cages that plied them with constant stimulation if their brain cells were to show evidence they were learning new skills.

But the brains of adult mice whose Nogo receptors were knocked out were showing signs of intensive learning, even when they were housed in cages that offered little stimulation.

The two sets of mice appeared in all respects the same in early childhood and adolescence: It was only with the transition to adulthood that the protein’s power to tame the brain’s constant rewiring act became evident.

Did the mice actually behave any differently when their brains were “reset” to teenage mode?

But there was one key behavioral difference between the groups: When researchers taught the mice to expect a shock when they heard a buzzer — a process called fear conditioning — adult mice whose brains were in “hard-wired” mode found it harder to adapt to changes intended to extinguish that fear. But fear-conditioned mice who had their Nogo receptors knocked out easily lost their fear reactions when researchers taught them they were in no danger.

Strittmatter suggests that if the brains of adult patients with stroke, PTSD or spinal-cord injury could recapture the plasticity of youth, they too might repair as quickly and thoroughly as youths do.

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