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Estrogen’s Protective Powers Reach the Brain
Possible role in preventing stroke
Edward R. Winstead

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Estrogen has potent protective effects in the adult and aging brain. These effects appear to involve genes that enhance the survival and function of neurons and may be mediated by estrogen receptors.

Menopause marks the end of a woman’s reproductive life, and the beginning of life with less estrogen. Estrogen is well known to play a role in bone health as well as in the cardiovascular, digestive, and immune systems and recent studies have suggested it may also benefit the brain. For instance, studies show that estrogen may enhance memory and cognition. Postmenopausal women taking estrogen appear less likely to develop Alzheimer’s, or may get a milder form of the disease later in life.

After a stroke: brain images from rats taking oil or estrogen. The white tissue represents stroke injury.

Phyllis M. Wise of the University of Kentucky College of Medicine is investigating a possible role for estrogen in protecting the brain from injury. At the meeting on Sex and Gene Expression she presented a study in rats showing estrogen’s protective effects and discussed possible mechanisms.

A synthetic hormone and surgery

Wise and her colleagues asked whether estrogen protects the brain when taken for several days prior to, or immediately following, injury such as a stroke. The researchers put rats whose ovaries had been removed on normal levels of a synthetic estrogen hormone, estradiol. A few days later, a surgeon inserted a tiny thread into the rat brains, effectively causing a stroke. The surgeon also operated on a control group of rats whose ovaries had been removed. These rats were given oil instead of estradiol.

The hormone treatment appeared to be protective. "The negative effects were significantly reduced in the mice taking estradiol," according to Wise. The rats that received estradiol only after the surgical injury did not seem to benefit. "Pre-treatment was critical," Wise says.

What is it about the hormone treatment that helped? One possibility is that the brain was protected by increased blood flow or more blood sugar caused by the estradiol. This turned out not to be the case.

Gene activation

Wise hypothesized that estradiol actually turns on genes that help brain cells survive trauma. She and her team compared the activity of genes in both the treated and untreated rats after injury. They looked first at a gene called Bcl-2 that is important to the survival and functioning of cells. Estradiol had been shown to increase the activity of Bcl-2 in tissues outside the brain, and Wise observed a similar effect in the brain. The hormone treatment seemed to prevent the loss of Bcl-2 activity that usually accompanies injury.

Wise also looked at the activity of the two estrogen receptor genes and found increased activity in response to injury in the treated mice. "We believe the estrogen receptors are involved," Wise reports. "Our studies are dedicated to figuring out if one is more important than the other in mediating the effects."

Future studies will look at estradiol’s effect on other genes and try to further define possible mechanisms.

See related GNN articles
»Sex Differences and Gene Expression in Autoimmune Disease
»Images of Imprinting

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The brain images are from "Estradiol protects against ischemic brain injury in middle-aged rats" by Phyllis M. Wise and Dena B. Dubal. Biology of Reproduction. In press.

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