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Studying the Effects of Estrogen on Memory

A new study from the University of Illinois has found that chronic exposure to estradiol, the main estrogen in the body, diminishes some cognitive functions: Rats exposed to a steady dose of the estrogen did not perform as well on tasks involving working memory and response inhibition.

The researchers were studying the effects of estradiol on activities regulated by the prefrontal cortex, a brain region that controls working memory — the ability to quickly and briefly recall information needed for a specific task, such as remembering a phone number. The prefrontal cortex also manages the ability to plan, to respond to changing conditions and to moderate behavior.

In the study, rats were trained to press one of two levers to obtain a food reward. The levels were taken away from the rat enclosure for a few seconds between trials, and the rats that switched between the levers received their just reward. Those that hit the same lever twice in a row got zilch. Rats exposed to estradiol performed worse than their counterparts on this task, the results showed.

A second set of tests measured the rats' patience; the rats had to wait 15 seconds before pushing a lever to get a reward. Again, those exposed to estradiol performed worse on this task than those that were not exposed.

"That's the test where we really saw the most striking effects with estradiol," said Susan Schantz, a professor of veterinary biosciences at Illinois and principal investigator on the study. The estradiol-treated rats "were not as good at waiting," she said.

Not that the researchers expected to find these results. The study had been designed to give them baseline data on the effects of soybean estrogens on cognitive function, so they could then compare the effects of chronic estradiol exposure to the effects of chronic exposure to genistein, a phytoestrogen found in soybeans and an increasingly common ingredient in supplements. "Women take them thinking they'll be a safe alternative to hormone-replacement therapy and they might help hot flashes," Schantz said.

In earlier studies, psychology professor Donna Korol, a collaborator on the current project, found that estradiol enhances some abilities, such as place or spatial learning. But it hindered others, such as methods of learning that rely on stimulus-response associations, or habit.

Multiple factors influence the effects of estradiol on the brain, Schantz said. The timing of the exposure, the types of brain functions or regions studied and the age of the test subjects can all generate different results, she said.

The researchers' report appears this week in the journal Behavioral Neuroscience.