Estrogen treatment had less beneficial effect on memory in active female mice

Estrogen treatment had less beneficial effect on memory in female mice that raced on running wheels and played with other toys than in mice raised in non-stimulating environments, according to a Yale study published this month.

Estrogen is a female hormone produced by the ovaries; it is responsible for secondary sexual characteristics in females and for the preparation of the uterus for implantation of the fertilized egg.

"We saw no beneficial effect of estrogen in the animals in cognitively and physically stimulating environments (also known as enriched environments)," said Karyn Frick, assistant professor of psychology and principal investigator on the study. "This fits in nicely with human data and might help to explain why studies of hormone replacement therapy (HRT) do not show beneficial effects for all women. Most studies of HRT use very well-educated women. These results might spur researchers to include a broader population with a greater variation in education and socioeconomic status."

All of the mice lived in standard housing conditions that contained other mice and no toys. However, enriched mice spent three hours each day in larger cages with running wheels, tubes, and other mouse toys. The toys were varied from day to day. At 10 weeks of age, the ovaries of the mice were removed to simulate the long-term estrogen losses seen in menopause. At six months of age, the mice were then treated with estrogen or a control substance and were tested in tasks measuring spatial memory and memory for objects.

"Animals raised in standard conditions showed significant spatial and object memory improvement when treated with a high dose of estrogen, whereas memory in animals in the enriched environment were unaffected or impaired by estrogen treatment," Frick said. "Among mice not treated with estrogen, enrichment treatment alone significantly improved spatial memory. The behavioral changes were also associated with alterations in a part of the brain critical for memory. These data suggest that estrogen benefits mice raised in un-stimulating environments more than those raised in cognitively and physically stimulating environments."

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