Yale University researchers reported Tuesday they have found a molecular mechanism by which estrogen improves memory, a finding that may aid the quest to improve cognition in aging women without the negative health effects of hormone therapy.
The issue of whether estrogen improves memory in women is still hotly debated. Recent studies have shown little or no benefit of hormone therapy in preventing memory loss or dementia among post-menopausal women. Yet many lab studies have shown the benefits of estrogen on memory and brain function in both animals and humans.
“No study has been able to directly link changes in the brain with changes in memory, so our study helps to fill in this gap,” said Karyn Frick, associate professor of psychology and senior author of the study.
The study, published in the Journal of Neuroscience, pinpoints a mechanism in the brain by which estrogen enhances memory in mice. If results hold in people, it could lead to therapies that could benefit memory in menopausal women, and possibly even men.
Frick’s team conducted a series of experiments that involved the hippocampus, a part of the brain critical for learning and memory. In one, they injected mice lacking ovaries with either a control substance or with estradiol, a potent form of estrogen, immediately after training in a memory task. Mice that received estradiol remembered better than mice that received the control injection, suggesting that estradiol plays an important role in memory consolidation.
Importantly, the investigators also showed that estradiol activates a specific molecule in the hippocampus, and drugs that blocked this molecule in the hippocampus completely prevented estradiol from enhancing memory. This novel finding pinpoints this molecule as a crucial step for estradiol to influence memory.
“Although the findings do not change overall debate on the use of estrogen therapy to reduce age-related cognitive decline, our study illustrates that specific molecules may be identified that are critical to estrogen’s ability to modulate memory,” Frick said. “Therefore, it may be possible to design drugs to target these molecules and directly affect memory. And since such drugs would not be hormones, they could produce the beneficial effects of estrogen treatment without the side effects of current hormone therapy.”
The National Institute on Aging funded study
Other authors include Stephanie M. Fernandez, Michael C. Lewis, Angela S. Pechenino, Lauren L. Harburger, Patrick T. Orr, Jodi E. Gresack, and Glenn E. Schafe
Citation: Neuroscience, Aug. 27, 2008