Some brain regions retain enhanced ability to make new connections

(Press-News.org) Contact information: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Some brain regions retain enhanced ability to make new connections In adults, some brain regions retain a "childlike" ability to establish new connections, potentially contributing to our ability to learn new skills and form new memories as we age, according to new research from Washington University School of Medicine in St. Louis and the Allen Institute for Brain Science in Seattle.

The scientists arrived at the new findings by comparing gene activity levels in different regions of the brain. They identified adult brain regions where genes linked to the construction of new connections between cells have higher activity levels. The same genes are also highly active in young brains, so the researchers called this pattern of gene activity childlike.

"We already knew that the adult human brain generally has more activity among these genes when compared with other closely related species, including chimpanzees and monkeys," said first author Manu S. Goyal, MD, a fellow in neuroradiology at Washington University. "Our new results connect this activity to a form of energy production known to be helpful for building biological structures, such as the new nerve cell branches needed to add connections in the brain."

Scientists believe that new links between brain cells help encode new memories and skills long after the brain stops growing.

The study appears Jan. 7 in Cell Metabolism.

Several years ago, senior author Marcus Raichle, MD, professor of radiology, psychology, neurology, neurobiology and biomedical engineering, was investigating the brain's voracious consumption of sugar and oxygen to make energy and enable other functions when he noticed that a few areas of the brain consumed sugar at exceptionally high rates. He and his colleagues later showed that this was because these regions were actively engaged in an alternative energy-making process called aerobic glycolysis.

"Aerobic glycolysis happens to be the form of sugar consumption favored by cancer cells and other rapidly growing cells," said Goyal. "This made us wonder if the brain regions that use aerobic glycolysis were also those that had the most childlike gene activity, namely those that help form new brain cell connections."

For the new study, Raichle collaborated with Michael Hawrylycz, PhD, a scientist at the Allen Institute for Brain Science. The institute's accomplishments include creating the Allen Human Brain Atlas, a database detailing the activity of genes in different parts of the brain and from people of different ages.

When researchers used the atlas to look at gene activity in brain regions with high rates of aerobic glycolysis, they found that these regions had more childlike gene activity than other brain regions. They also identified more than 100 genes that consistently were more active in these regions than in others.

As part of the study, Goyal also analyzed data from earlier research by other scientists to show that there is more aerobic glycolysis throughout the brain in young children.

"In the adult brain, aerobic glycolysis accounts for about 10 to 12 percent of overall sugar consumption," he said. "In young children, aerobic glycolysis accounts for 30 to 40 percent of overall sugar usage."

Aerobic glycolysis is less efficient for energy production than oxidative glycolysis, the alternative method that uses oxygen and sugar. But scientists think the former is a better source of energy for rapid growth.

"Even in adults, there are parts of the brain that still are rapidly changing and adapting, and that's likely why aerobic glycolysis continues to be used in the adult brain," Goyal said.

The researchers now are studying whether problems in specific brain cells that use aerobic glycolysis contribute to neurodevelopmental problems such as autism or mental retardation or to neurodegenerative disorders like Alzheimer's disease.

"The ability to support the metabolic requirements of adult brain cells to create new connections may one day be important for treating brain injuries and neurodegenerative disorders," Goyal explained. "We have a lot of work to do, but this is an intriguing insight."

### This research was supported by funding from the National Institutes of Health (NIH) (P50 NS006833 to M.E.R. and A.Z.S.) and the National Institute of Neurologic Disorders and Stroke (P30 NS048056 to A.Z.S.). The Allen Human Brain Atlas is supported in part by award numbers 1C76HF15069-01-00 and 1C76HF19619-01-00 from the Department of Health and Human Services Health Resources and Services Administration.

Goyal MS, Hawrylycz M, Miller JA, Snyder AZ, Raichle ME. Aerobic glycolysis in the human brain is associated with development and neotenous gene expression. Cell Metabolism, Jan. 7, 2014.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

The Allen Institute for Brain Science is an independent, 501(c)(3) nonprofit medical research organization dedicated to accelerating the understanding of how the human brain works in health and disease. Using a big science approach, the Allen Institute generates useful public resources used by researchers and organizations around the globe, drives technological and analytical advances, and discovers fundamental brain properties through integration of experiments, modeling and theory. Launched in 2003 with a seed contribution from founder and philanthropist Paul G. Allen, the Allen Institute is supported by a diversity of government, foundation and private funds to enable its projects. Given the Institute's achievements, Mr. Allen committed an additional $300 million in 2012 for the first four years of a ten-year plan to further propel and expand the Institute's scientific programs, bringing his total commitment to date to $500 million. The Allen Institute's data and tools are publicly available online at http://www.brain-map.org.