Restoring Creation of Lasting Memories in Older or Damaged Brains

By Sondra Forsyth

Aging or impaired brains can once again form lasting memories if an enzyme that applies the brakes too hard on a key gene is lifted, according research done University of California, Irvine and Mount Holyoke neurobiologists.

A release from the university quotes senior author Marcelo Wood, UCI’s Francisco J. Ayala Chair in Neurobiology & Behavior, who presented the findings at the American Association for the Advancement of Science’s annual meeting, in Austin, Texas in February 2018, as saying, “What we’ve discovered is that if we free up that DNA again, now the aging brain can form long-term memories normally. In order to form a long-term memory, you have to turn specific genes on. In most young brains, that happens easily, but as we get older and our brain gets older, we have trouble with that.”

That’s because the six feet of DNA spooled tightly into every cell in our bodies has a harder time releasing itself as needed, he explained. Like many body parts, “it’s no longer as flexible as it used to be.” The stiffness in this case is due to a molecular brake pad called histone deacetylase 3, or HDAC3, that has become “overeager” in the aged brain and is compacting the material too hard, blocking the release of a gene called Period1. Removing HDAC3 restores flexibility and allows internal cell machinery to access Period1 to begin forming new memories.

Researchers had previously theorized that the loss of transcription and encoding functions in older brains was due to deteriorating core circadian clocks. But Wood and his team, notably postdoctoral fellow Janine Kwapis, found that the ability to create lasting memories was linked to a different process – the overly aggressive enzyme blocking the release of Period1 – in the same hippocampus region of the brain.

That’s potentially good news for developing treatments. “New drugs targeting HDAC3 could provide an exciting avenue to allow older people to improve memory formation,” Wood said.

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Researchers from UC Davis and Mount Holyoke College contributed to the work. Funding was provided by the National Institute on Aging, the National Science Foundation, the Defense Advanced Research Projects Agency, the French National Institute of Health & Medical Research and the Novo Nordisk Foundation.

About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 30,000 students and offers 192 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit http://www.uci.edu.