Flip of a single molecular switch makes an old brain young


The flip of a single molecular switch helps create the mature neuronal connections that allow the brain to bridge the gap between adolescent impressionability and adult stability. Now Yale School of Medicine researchers have reversed the process, recreating a youthful brain that facilitated both learning and healing in the adult mouse.

Scientists have long known that the young and old brains are very different. Adolescent brains are more malleable or plastic, which allows them to learn languages more quickly than adults and speeds recovery from brain injuries. The comparative rigidity of the adult brain results in part from the function of a single gene that slows the rapid change in synaptic connections between neurons.

By monitoring the synapses in living mice over weeks and months, Yale researchers have identified the key genetic switch for brain maturation a study released March 6 in the journal Neuron. The Nogo Receptor 1 gene is required to suppress high levels of plasticity in the adolescent brain and create the relatively quiescent levels of plasticity in adulthood. In mice without this gene, juvenile levels of brain plasticity persist throughout adulthood. When researchers blocked the function of this gene in old mice, they reset the old brain to adolescent levels of plasticity.

“These are the molecules the brain needs for the transition from adolescence to adulthood,” said Dr. Stephen Strittmatter. Vincent Coates Professor of Neurology, Professor of Neurobiology and senior author of the paper. “It suggests we can turn back the clock in the adult brain and recover from trauma the way kids recover.”

Rehabilitation after brain injuries like strokes requires that patients re-learn tasks such as moving a hand. Researchers found that adult mice lacking Nogo Receptor recovered from injury as quickly as adolescent mice and mastered new, complex motor tasks more quickly than adults with the receptor.

“This raises the potential that manipulating Nogo Receptor in humans might accelerate and magnify rehabilitation after brain injuries like strokes,” said Feras Akbik, Yale doctoral student who is first author of the study.

Researchers also showed that Nogo Receptor slows loss of memories. Mice without Nogo receptor lost stressful memories more quickly, suggesting that manipulating the receptor could help treat post-traumatic stress disorder.

“We know a lot about the early development of the brain,” Strittmatter said, “But we know amazingly little about what happens in the brain during late adolescence.”

Other Yale authors are: Sarah M. Bhagat, Pujan R. Patel and William B.J. Cafferty

The study was funded by the National Institutes of Health. Strittmatter is scientific founder of Axerion Therapeutics, which is investigating applications of Nogo research to repair spinal cord damage.


Tony Pietrantonio Knockout


Tony Pietrantonio was unfortunate enough to be on the receiving end of a knockout punch from Lavarn Harvell during their light heavyweight boxing match in Atlantic City, New Jersey

Pietrantonio, 34, came crashing down on to the canvas in the third round after receiving the blow, which a well-timed photo captured perfectly, conveying the sheer impact of the punch.

The punch was so hard that Pietrantonio’s face became heavily distorted and his mouth looked like it was about to twist off his face. Even his flapping ears appeared to absorb the full force of the blow.

Harvell, 23, said after the fight: “I felt that punch all the way up my shoulder and back, so I knew he wasn’t getting up.”

He was completely right. The devastating blow, delivered after 31 seconds in the third round, gave him the fight. It was his second straight knockout in four weeks.

Pietrantonio, who only agreed to fight three days beforehand, had previously won six of the 17 bouts in his boxing career, but did not stand a chance after the dramatic jab from Harvell.

He was unconscious as he hit the ground, prompting referee David Fields to immediately stop the fight and call for medical assistance.

After a few minutes, Pietrantonio was then able to climb on to the stool in his corner and eventually shook off the injury to leave the ring under his own power.