Synaptic Plasticity and Memory Affected by Neuron-Derived Estrogen

Estrogen in the brain is important to keep neurons communicating and memories being made, scientists from Medical College of Georgia at Augusta University reported earlier this month in the Journal of Neuroscience.

Neurons in both males and females make estrogen and the scientists have shown that when they don't, their brains have significantly less dense spines and synapses—both key communication points for neurons—in the forebrain.

"We think this shows estrogen has a clear role in synaptic plasticity, how the neurons communicate and in memory," says Dr. Darrell Brann, interim chair of the department of neuroscience and regenerative medicine.

Brann and his colleagues found that mice whose neurons don't make estrogen have impaired spatial reference memory—like a baseball player not knowing where home plate is and what it means to get there—as well as recognition memory and contextual fear memory—so they have trouble remembering what's hazardous. Restoring estrogen levels to the brain area rescues these impaired functions, Brann and his colleagues report.

It was known that aromatase, the enzyme that converts testosterone to estrogen, was made in the brain's hippocampus and cerebral cortex in a variety of species that includes humans, Brann says, and that they all can have memory deficits when aromatase is blocked. Patients who take an aromatase inhibitor for estrogen-dependent breast cancer also have reported memory problems.

In mouse studies, the team knocked aromatase out of the forebrain, which includes the hippocampus and the cerebral cortex. They also depleted aromatase in the excitatory neurons  in the forebrain as a way to focus on the role of estrogen produced by these brain cells. The bottom line was a 70-80% decrease in aromatase and estrogen levels in the neurons in these areas of the brain. The other bottom line: "The knockout mice can't remember as well as the normal mice," Brann says.

There are many blanks left to fill in before the natural process will be understood so treatment potential could be explored, he says. That includes learning more about what is regulating brain aromatase, whether brain estrogen levels decrease with normal aging and, if they do, what could be used to increase aromatase and estrogen production in the brain, Brann adds.