UAB Researchers Break New Ground On How Memory Works

BIRMINGHAM, Ala. – Researchers at UAB (University of Alabama at Birmingham) have discovered that a chemical reaction in cell DNA thought to be involved only in embryonic cell development and differentiation is also required for memory formation.

“During embryonic development, cells use two major techniques to determine what type of cell they will be…the chemical change known as gene methylation, and another physical change in the three-dimensional structure of DNA known as chromatin modification,” said J. David Sweatt, Ph.D., chair of the Department of Neurobiology and director of the Evelyn F. McKnight Brain Institute at UAB. Sweatt is lead author of the study, which appears in the March 15 issue of Neuron.

“Our research is the first to show that DNA methylation also takes place in the neurons of adult brains in response to life experiences, allowing for memory formation based on learned behavior,” he said.

Sweatt says these findings open new avenues for research into memory disorders and into drug development for agents that might boost memory function. Sweatt also says the knowledge that adult brains do undergo methylation also has applications for the study of psychiatric disorders such as schizophrenia, which may be caused by improper regulation of methylation.

“The chemical modification of DNA is much more universal than we thought, continuing into adulthood rather than strictly being a function of developing cells,” Sweatt said. “Neurons have to make some sort of permanent change in their molecular properties in order to preserve memory, and methylation appears to be a critical mechanism for triggering that change.”

Sweatt, along with Courtney Miller, Ph.D., a post-doctoral fellow in neurobiology, studied gene methylation in the hippocampus region of rat brains. The hippocampus has long been known to be integral to memory, and is a known site for memory disruption in memory disorders like Alzheimer’s Disease. The researchers conditioned memories in rats by inducing mild shocks when the rats were placed in a training chamber. They could then test whether the rats remembered the conditioning by observing their reaction when placed in the chamber again.

Using drugs that inhibit methylation, the researchers showed that methylation was necessary for rats to form such memories. They also used ultra-sensitive DNA measurement techniques, similar to those used in some police forensic laboratories, to directly demonstrate altered DNA methylation in the brains of trained animals.

The research was supported by the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, parts of the National Institutes of Health; the American Health Assistance Foundation and the Evelyn F. McKnight Brain Research Foundation.

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