University of Kentucky College of Medicine researchers have determined that one specific estrogen receptor, called ERa, is a critical link in mediating the protective effects of estradiol in brain injury. The study was led by Phyllis Wise, Ph.D., professor and chair, and Dena Dubal, graduate student in the M.D./Ph.D. program, of the Department of Physiology, UK College of Medicine, and appears in the Feb. 6 online issue and the Feb. 13 issue of the Proceedings of the National Academy of Sciences.
Previous research by Wises team has demonstrated that estradiol, a type of estrogen, protects against brain injury (including injury from stroke), neurodegeneration and cognitive decline. The UK College of Medicine research team examined whether estrogen receptors are critical for estrogens neuroprotective effects. The team focused on two estrogen receptor types, ERa and ERb. Using animal models in which one of the receptor types had been deleted, they demonstrated that when ERa is absent, estradiol no longer has protective effects in any area of the brain. But when ERb is absent, estradiol still provides effective neuroprotection.
We have demonstrated that future research and development for therapies that capitalize on estradiols neuroprotective effects should focus on ERa, Wise said. These results have tremendous implications for developing therapeutic agents for treating brain injuries.