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Scientists Report that Enzyme Aromatase has Big Impact in Healthy and Injured Brains


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An enzyme that converts testosterone to estrogen appears to have a significant impact on a healthy and injured brain, scientists report.

There’s a growing body of evidence that in the healthy brain, aromatase, and the estrogen it enables neurons to produce, help keep our minds sharp and flexible. Now scientists are learning that with injury, aromatase and estrogen expression seem to shift to cells in the brain called astrocytes.

These cells support and nurture stressed brain neurons, said Dr. Darrell Brann, Regents’ Professor and Vice Chairman of the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Georgia Regents University.

Numerous studies, including those in Brann’s lab, have shown this shift in aromatase/estrogen expression from neurons to astrocytes following injury.

In Brann’s case, the studies have been in the hippocampus, a center of learning, memory, and emotions. When he used a drug to reduce astrocyte’s aromatase expression in that region, increased inflammation and brain damage resulted.

A new $1.8 million grant from the National Institute of Health will allow him to further clarify the role of aromatase and estrogen in injury and health and (hopefully) discover therapies that can increase the brain’s apparent effort to heal.

The studies are conducted with several laboratory mice, one with aromatase removed from neurons, another with it missing in astrocytes, and a third with aromatase lacking in both brain cell types.

The mice were developed by Brann’s lab in collaboration with Dr. Ratna K. Vadlamudi, Professor of Obstetrics and Gynecology at the University of Texas Health Sciences Center.

“We will be able to tell the cell-specific function of estrogen,” Brann said. “We want to know what happens when they don’t have it. We’ll study the plasticity, the connectivity of neurons in these knockouts, and we’ll consider their cognitive function using behavioral tests.”

They’ll also see what happens to inflammation and recovery when aromatase expression can’t increase as it probably should following injury.

Brann is not surprised that usually supportive astrocytes levels would increase the following injury and thinks estrogen is critical to the expanded role.

“In a non-injury situation, we see it mostly in the neurons, so it much [sic] has some functions such as plasticity and connectivity normally,” he said.

Following injury, when astrocytes start making aromatase then estrogen, the emphasis appears to shift to protection and recovery.

He added that as with every built-in protective mechanism, astrocyte support is not 100% foolproof; sometimes natural recovery mechanisms get overwhelmed by the extent of the injury.

However, Brann hopes that, in addition to better understanding what estrogen does in the brain typically and following injury, the new studies will point toward new therapies that augment the apparent natural recovery effort.

Neurons highly express aromatase in a healthy hippocampus.

Following a traumatic injury or stroke, the high expression appears to shift to astrocytes, a type of glial cell, found in abundance in the central nervous system that generally provides support and cushion for neurons.

Astrocytes are known to become more active after brain injury, unleashing more supportive, healing factors that many scientists are convinced also help lower inflammation and boost their protection of neurons.

However, if astrocytes remain activated for too much time, they can also cause problems, including gliosis, which is mostly a scar-like wad of glial cells in the area living neurons previously occupied.

“You have to regulate all these factors being released tightly,” Brann said.

Even in culture, neurons will connect and communicate, but scientists add an aromatase inhibitor to the mix, which blocks connectivity.

Some of the initial in vivo studies in zebra finches demonstrated that aromatase levels increased following a brain injury, which also supports a protective role for the protein. More brain damage results when aromatase inhibitors are given.

“There seemed to be more inflammation,” Brann said.

Part of what he wants to learn about how estrogen aids brain connectivity and plasticity, is exploring whether it regulates brain-derived neurotrophic factor, which is known to have a role in both.

Brann also plans to pursue the role of aromatase and estrogen in neurodegenerative diseases, such as Alzheimer’s, where there is some early evidence that missing aromatase increases plaque development.

Naturally high estrogen levels in premenopausal women have long been considered protective of stroke as well as heart attacks and other maladies.


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