USC Findings Explain Estrogen's Ability To Enhance Memory

"Previous studies have suggested that the hormone estrogen delays the onset of Alzheimer's disease, and several million post-menopausal women are taking estrogen supplements for that reason," says USC neurophysiologist Richard F. Thompson, Ph.D. "Our research reveals a chemical mechanism that could explain how the delay in onset occurs."

Dr. Thompson and his colleagues measured the excitability and long-term potentiation between neurons from the brain of a rat, both before and after exposing slices of the brain's hippocampus to estrogen. The researchers looked specifically at the hormone's influence on a neurotransmitter called glutamate and two of its receptors, NMDA and AMPA. Neurotransmitters are chemicals that mediate the transmission of electrical impulses across the synapses between neurons.

"The estrogen activated both receptors within minutes -- causing a lasting increase in neuronal activity," Thompson reports. "Estrogen also enhanced the process of long-term potentiation. Activating the NMDA receptor apparently initiates long-term potentiation, and the AMPA receptors maintain it."

Since its discovery more than two decades ago, long-term potentiation has been intensively studied in hundreds of research laboratories around the world. The phenomenon is a long-lasting increase in neuronal responses in the hippocampus, a major structure in the forebrain of all mammals. It is thought to be a mechanism of memory shortage in the brain.

Thompson believes that learning more about the mechanism of long-term potentiation could lead to highly refined treatments for Alzheimer's disease. Researchers are studying compounds that are similar or related to estrogen in the hope of finding a drug precisely targeted for the treatment of disease while avoiding unwanted side-effects.

USC neurogerontologist Victor W. Henderson, M.D., who was among the first to conduct epidemiological studies finding that estrogen delays the onset of Alzheimer's disease in post- menopausal women, calls Thompson's study significant. "The inference is that estrogen has effects on learning and cognitive function that go far beyond the hormone's reproductive role," Dr. Henderson says.

The estrogen study was published in the February issue of the Journal of Neurophysiology. Funded by grants from the National Institutes of Health, the National Institute on Aging and the National Science Foundation, the research is part of an ongoing project led by USC neurogerontologist Caleb E. Finch, Ph.D., as principal investigator.

Richard F. Thompson, a professor of biological sciences and psychology in the USC College of Letters, Arts and Sciences, directs USC's Program in Neural, Informational and Behavioral Sciences. He holds the college's William M. Keck Chair in Biological Sciences and Psychology.

Other USC researchers participating in the study include Roberta D. Brinton, associate professor of molecular pharmacology and toxicology at the USC School of Pharmacy; Jimin Xu, a research associate in the molecular pharmacology; Theodore W. Berger, a professor of biomedical engineering at the USC School of Engineering; Xiaping Xie, a research assistant professor in biomedical engineering; and Michael Foy, a professor of psychology at Loyola Marymount University who also works as a research associate in the USC Program in Neural, Informational and Behavioral Sciences.