Estrogen receptors play anti-inflammatory role in the brain

http://www.eurekalert.org/pub_releas...-erp050911.php

Researchers have uncovered an unexpected role for estrogen receptors in the brain in keeping inflammation under control. The findings reported in the May 13 issue of the Cell Press journal Cell may have important implications for the treatment of multiple sclerosis (MS) and many other neurodegenerative diseases. They might also help to explain why women are three times more susceptible to developing MS than men are, researchers say...


Estrogen receptors are primarily known to activate programs of gene expression, he explained. In this case, however, estrogen receptors are critical for turning off genes that would otherwise lead to chronic inflammation...

The estrogen receptor (ER)... (is) related receptors known as ERβ found in cells of the brain known as microglia and astrocytes. Microglia serve as sentinels of infection and injury in the brain... astrocytes also sense infection and injury, and amplify the immune reaction initiated by microglia.


When levels of either ADIOL or ERβ were experimentally reduced, cells and animals showed an exaggerated inflammatory response...

Although MS is a very complicated disease, the findings suggest drugs targeted at the ERβ receptors might effectively shut down the inflammation... The same principle might also work in the treatment of other neurodegenerative conditions associated with inflammation, including Parkinson's, Alzheimer's and HIV-associated dementia.

The findings might also help to explain the strong sex bias in MS, which disproportionately affects relatively young women...



In addition to explaining why females develop MS more often than males, Gosselin and Rivest continued, the findings also suggest that birth control medications and environmental factors such as estrogen analogs derived from plants might also promote development of the disease.

"The possibility arises from our study that estradiol can antagonize the anti-inflammatory effects of ADIOL," Glass said. "This may lead to a shift in the balance from anti-inflammatory to inflammatory."

Glass and Saijo say they plan to further explore the role of this pathway in other neurodegenerative diseases..