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Animal studies prove hormone replacement therapy improves memory, report Pitt researchers

University of Pittsburgh Medical Center

PITTSBURGH, Nov. 5 - For estrogen to enhance learning and memory, nerve cells in the brain called cholinergic neurons are essential to the process, suggest animal studies performed by researchers from the University of Pittsburgh School of Pharmacy and reported in the November issue of Hormones and Behavior, the official journal of the Society for Behavioral Neuroendocrinology.

"Estrogen replacement in postmenopausal women has important effects on mood and cognition. This research was focused on trying to understand what estrogen does in the brain to reduce the effects on brain aging and cognitive decline," stated Robert Gibbs, Pharm.D., associate professor of pharmaceutical sciences at the University of Pittsburgh School of Pharmacy.

In the study, rats had their ovaries removed and some of the animals had specific cholinergic neurons destroyed. A few weeks after surgery, most of the animals were put on estrogen replacement therapy (ERT), while some were not. Four weeks after ERT, the animals were placed several times in a maze to test their memory and performance. Rats that had their ovaries removed with subsequent ERT outperformed rats on various tasks without ERT. The ability of estrogen to enhance performance was lost in animals that had specific cholinergic neurons removed.

"This tells us that the cholinergic neurons are necessary for estrogen to enhance performance in this model," explained Dr. Gibbs.

"We have shown, as in previous studies, that acute and short-term estrogen replacement can significantly enhance the functional status of cholinergic neurons. These results give us hope that estrogen may help to significantly reduce the risk of Alzheimer's-related dementia in postmenopausal women, possibly by affecting these cholinergic neurons," added Dr. Gibbs.

While there have been some studies on the effects of hormone replacement therapy in cognitive decline in postmenopausal women, many experts say further studies need to be done. Sarah L. Berga, M.D., professor of obstetrics, gynecology and reproductive sciences and psychiatry at the University of Pittsburgh School of Medicine, who was not officially part of this study, notes this evidence adds to the growing body of cellular and epidemiological data suggesting that estrogen use after menopause guards against the development of dementia.

"The study also suggests why starting estrogen after dementia has developed is ineffective. For estrogen to work, the neurons must be alive and working," stated Dr. Berga.

"I would hesitate to say that these results extend to humans, but the findings are encouraging because they help pinpoint a specific biological effect that may underlie beneficial effects on cognitive performance," concluded Dr. Gibbs.



Maureen McGaffin
Lisa Rossi
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