Memory & Mood

UAB Neurobiologist Breaks New Ground in Memory Disorder Research

If we stop to think about it, we realize that our memories are at the core of our individual personalities and identities — they’re the unique tapestries that weave together the story of our life experience. Yet for millions of Americans with Alzheimer’s disease or other forms of dementia, memories seem hopelessly and mysteriously lost. But are the memories really gone — or is it possible that they could somehow be retrieved?

UAB neurobiologist David Sweatt, PhD, is conducting groundbreaking clinical research that may someday lead to the development of effective medications for treating age-related memory dysfunction. “In conducting laboratory research with mice and other animals, we’re interested in determiniming how memory is formed and stored and what goes wrong with age-related memory dysfunction,” explains Dr. Sweatt, who is chairman of the UAB Department of Neurobiology and director of UAB’s Evelyn F. McKnight Brain Institute. “We’ve identified compounds that improve the formation of long-term memories and may hold promise for the development of future treatments for memory disorders such as Alzheimer’s disease and dementia.”

Groundbreaking Discoveries in How Memories are Formed

A few years ago, Dr. Sweatt and his colleagues at UAB discovered that learning and the formation of long-term memory involve changes in the three-dimensional structure of DNA and associated proteins in the brain. Deep within brain cells, or neurons, DNA strands are tightly coiled around proteins called histones — much like strands of thread wound around a spool.

“We discovered that when the DNA strands are loosened, genes involved in learning and memory are exposed and can be switched on. This process creates new pathways for learning, memory formation and retrieval,” Dr. Sweatt explains.

In people with memory disorders, this process seems to be disrupted. “Our understanding of this process led to the idea of developing compounds that would manipulate the 3-D structure of DNA and its associated proteins within neurons. We hoped these compounds would improve learning and memory formation in the laboratory.”

Dramatic Results from a Revolutionary Compound

The compounds Dr. Sweatt tested — called HDAC inhibitors — were given to normal mice in the laboratory before learning exercises that required them to remember and repeat certain tasks. “The mice had improved memory formation after being given the HDAC inhibitors,” says Dr. Sweatt. “We’re in the process of evaluating the effects of these compounds on aged animals.”

Last year, a group of researchers at MIT gave the HDAC inhibitors Dr. Sweatt utilized to a group of genetically engineered mice with damaged brain cells. “The inhibitors led to significant improvements in learning and memory formation in these mice, which was an exciting finding,” says Dr. Sweatt. Several biotech companies and academic groups are beginning to implement further testing of HDAC inhibitors. “We believe these compounds hold promise for developing new therapies for age-related memory dysfunction, Alzheimer’s disease, and other forms of memory loss.”