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January 28, 2008
Genes Influence Blood Lipid Levels and Heart Disease Risk
Blood levels of lipids like cholesterol and triglycerides are important risk factors for coronary artery disease. Scientists know about certain lifestyle factors—such as smoking, diet and physical activity—that affect blood lipid levels, but the role of genetics hasn't been well understood. A large study has now revealed more than 25 genetic variants in 18 genes connected to blood cholesterol and lipid levels. The finding may lead to new strategies for treating and preventing coronary artery disease.
Animal studies have revealed that, when long-term memories are recalled, they become fragile and changeable. New proteins must be produced to reconsolidate retrieved memories and return them to long-term storage in the brain. Recalling a memory, then, opens a window of opportunity for that memory to be changed—what researchers call a "reconsolidation window." Earlier studies showed that certain drugs can block reconsolidation, but using such drugs in people can be problematic.
Earlier this year, a team led by Dr. Joseph LeDoux of New York University (NYU) developed a way to erase a fear memory in rats without using drugs. The researchers first conditioned rats to fear a tone by pairing it with shocks. The animals then underwent a process to erase the fear, called extinction training, in which the tone was repeatedly presented without shocks. Both an initial re-exposure to the shock and the subsequent timing of extinction training proved critical. Fear of the stimulus was erased only in rats trained within a 6-hour reconsolidation window after re-exposure to the feared tone. Fear responses returned in animals if the training began more than 6 hours after re-exposure, when the memory had apparently already solidified.
In the new study, a team led by LeDoux's colleague at NYU, Dr. Elizabeth Phelps, set out to see if extinction training could similarly erase a fear in people. Their work, which was funded by NIH's National Institute of Mental Health (NIMH) and the James S. McDonnell Foundation, appeared online on December 9, 2009, in Nature.
The researchers conditioned human participants to fear colored squares by pairing them with mild wrist shocks. A day later, the memory was first reactivated by re-exposing participants to the feared squares. Measures of nervous system arousal confirmed that the participants experienced a fear response. Extinction training—repeated exposures to the colored squares without shocks—followed.
A day later, the fear response was banished only in human participants who underwent extinction training soon after fear reactivation. Those whose training began more than 6 hours later remained afraid of the squares. So did a control group that received extinction training without first experiencing reactivation of the fear memory.
To gauge the long-term effects of the training, participants were tested a year later. They were given 4 unsignalled shocks to re-instate their fear and then shown the colored squares. Only those who had undergone extinction training within the reconsolidation window were largely spared a fear response to the squares.
“This adaptive update mechanism appears to have evolved to allow new information available at the time of retrieval to be incorporated into the brain's original representation of the memory,” explains Phelps. “Our memory reflects our last retrieval of it rather than an exact account of the original event.”
“Inspired by basic science studies in rodents, these new findings in humans hold promise for being translated into improved therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder,” says NIMH Director Dr. Thomas R. Insel.