UF’s McKnight projects combat memory maladies

University of Florida research with potential to quickly pay off with new treatments or ways to diagnose memory problems will get a boost from the Evelyn F. and William L. McKnight Brain Institute. Three UF scientists will receive $125,000 each for innovative projects to fight memory loss in older adults, MBI Executive Director Dennis Steindler, Ph.D., has announced.

“This initiative called for innovative and high-payoff ideas to solve age-related memory loss,” Steindler said. “We wanted out-of-the-box, state-of-the-art approaches, rooted in cellular, genetic, molecular and behavioral neuroscience.” Grant awardees aim to create a brain-scanning method to test drug treatments, to solve the mysteries of how brain cells age, and to develop neuroprotective drugs.

The projects further the mission of the late William L. McKnight, who served 59 years as chairman of 3M company, and his wife Evelyn F. McKnight, a former nurse who was deeply interested in why memory often fades as people age. The Brain Institute was named for the McKnights in May 2000, after the McKnight Brain Research Foundation board of trustees gifted UF with $15 million to support aggressive research.

Awardees include David Loring, Ph.D., a neurology professor in the College of Medicine; Leonid Moroz, Ph.D., an associate professor of neuroscience and zoology at UF’s Whitney Laboratory for Marine Bioscience; and Hendrik Luesch, Ph.D., an assistant professor and medicinal chemist in the College of Pharmacy. Loring wants to test the effectiveness of memory-loss therapies by applying a new statistical technique to a standard brain-scanning method called functional Magnetic Resonance Imaging, known as fMRI.

Traditional thought holds that when older people lose the ability to bank new memories, it may be because of deterioration in the brain’s temporal lobe.

But Loring believes it is possible that some older people actually lack the attention span to log new information into their memory, which places the problem in the prefrontal cortex — the brain’s attention center — not the temporal lobe.

He will work with Kimford Meador, M.D., a professor of neurology and director of the epilepsy and clinical Alzheimer’s programs, and Frank Bova, Ph.D., a physicist and professor of neurosurgery, to use new fMRI techniques to literally “watch” activity inside the brains of human volunteers as they respond to memory-related tasks.

While Loring and colleagues hope to pinpoint the regions of the brain that contribute to successful memory formation and develop a technique to test the effectiveness of drugs used to fight memory loss, Moroz is attempting to determine why some brain cells age more quickly than others.

Answers may come from the inconspicuous sea slug Aplysia californica. This ocean creature has the largest neurons in the animal kingdom, creating a simple memory-forming network that is easily studied.

Analyzing the biochemical products that result when the genes of Aplysia neurons express themselves may reveal markers for human memory function and provide information regarding a neuron’s “life span.” Moroz wants to know how neuron longevity affects memory and why specific neurons age at different rates.

“We have all the tools in our hands; the problem is combining the right people with the right cells to answer the question of what kind of genes contribute to long-term memory formation,” Moroz explained. “Nobody really understands on the level of specific cells how many genes work together. We are excited because this is the first time we will be able to monitor all genes in specific neurons.”

Results from Moroz’s research could mean new drugs to target specific cells in the brains of those suffering from age-related memory loss. “We want to know, do different neurons learn differently, and if they do, do they age differently? Put these puzzle pieces together and you can put together new therapies,” Moroz said. Meanwhile, Luesch, a medicinal chemist, seeks to identify proteins that can be modulated by drugs to activate protective genes to prevent neurological age-related disorders.

Collaborating with Alfred Lewin, Ph.D., a professor of molecular genetics and microbiology with the UF College of Medicine, and researchers at Scripps Florida, Luesch will screen genomewide libraries of DNA to find genes that regulate the synthesis of neuroprotective enzymes — proteins that cause or speed up chemical reactions. Initial screenings will be conducted with researchers at Scripps Florida, followed by detailed studies at UF. The award will allow Luesch to hire a postdoctoral researcher and to acquire instruments for more efficient analysis and gene validation.

“The McKnight Foundation grant will further the opportunity for collaboration with Scripps Florida and among colleges at the University of Florida,” Luesch said.

Strengthening research alliances is an important aspect of the McKnight grants, Steindler said.

“The grants allow us to advance the science being done in this institute through collaborations with investigators around the world,” Steindler said. “It’s important work. As we age, our memory is at risk. If we can devise novel interventions or enhance memory capabilities during the aging process, all of us will benefit.”