Scientists ID piece to brain's 'planner'

ou can teach an older brain new tricks, Medical Center scientists have discovered, becoming the first to show that boosting a specific molecule can help the brain rewire itself when faced with new experiences.

In a pair of overlapping studies that used a line of mice genetically engineered at Rochester, neuroscientists have pinpointed nerve growth factor (NGF) as a key molecule in the brain's ability to reorganize itself to learn.

"These studies demonstrate that giving the brain a workout definitely has an impact on brain structure at the molecular level," said first author Andrew Brooks, research assistant professor of neurology in the Center on Aging and Development. "Using your brain is a good thing. Maybe someday we'll know enough about how the brain stores and retrieves information to be able to help prevent people from losing their cognitive abilities prematurely, as we see in some neurodegenerative diseases."

The mice for each study--one published in the Proceedings of the National Academy of Science and the other in Human Gene Therapy --were modified using a gene transfer technology developed by Howard Federoff, director of the Center on Aging and Development and the principal investigator of the study.

Engineered so that cells in each mouse's hippocampus, a part of the brain vital to memory and learning, would carry extra copies of a gene that makes NGF, the mice develop as normal mice. But when they reach adulthood after about three months, the NGF gene turns on, boosting the amount of NGF in those cells within the hippocampus.

The scientists ran those mice and their normal counterparts through an experimental set-up designed with collaborator Deborah Cory-Slechta, dean of research and professor and chair of environmental medicine.

Divided into three groups, some mice spent their days simply milling about, others completed simple rote tasks such as running through the same maze day after day, and the third group was continually challenged with a new learning task--navigating a new maze.

Researchers found that the combination of increased NGF and a challenging learning environment led to the development of new neuronal connections in an area of the brain vital for memory and learning. The NGF-producing mice that were challenged the most became the quickest, most adept learners. The changes lasted for at least as long as the experiment continued, about eight months--well into middle age for a mouse.

The changes took place in an area known as the basal forebrain; the bundle of nerves connecting this area and the hippocampus are vital for learning and memory. The two areas work in sync, with neurons from the forebrain stimulated by molecules such as NGF that are made in the hippocampus.

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