Estrogen made by important neurons to create memories


Estrogen made by important neurons to create memories

Dr. Darrell Brann and graduate student Yujiao Lu Credit: Phil Jones, Senior Photographer, Augusta University

Scientists report that estrogen in the brain is important for neurons to remain in communication and to allow memorization.

Neurons in men and women produce estrogen and scientists have shown that, when they do not, their brains have significantly less dense thorns and synapses – two key communication points for neurons – in most of their brains, called forebrain.

"We believe this shows that estrogen plays a clear role in synaptic plasticity, in the way neurons communicate and in memory," said Dr. Darrell Brann, Acting Director of the Department of Neuroscience and Regenerative Medicine. Medical College of Georgia, Augusta University.

Brann and his colleagues have found that mice whose neurons do not make estrogen have an altered spatial reference memory – such as a baseball player not knowing where the marble is and what it means to get there – as well memory of recognition and the memory of contextual fear – having trouble remembering what is dangerous – they report in the Journal of Neuroscience.

Restoring estrogen levels in the brain area saves these impaired functions, report Brann and his colleagues.

It is known that aromatase, the enzyme that converts testosterone to estrogen, has been manufactured in the hippocampus and cerebral cortex of a variety of species including humans, explains Brann, and that they can all have a memory deficit when the aromatase is blocked. Patients taking an aromatase inhibitor for estrogen-dependent breast cancer also reported memory problems.

So for these studies in the mouse, they knocked out the anatomy of the forebrain, which includes the hippocampus, which plays a role in long-term memory and spatial memory, as well as the cerebral cortex, important for memory, attention, consciousness and thought. .

They only deplete aromatase in excitatory neurons – called exciters because they help to act as thought – in the forebrain as a way to focus on the role of estrogen produced by these brain cells.

The end result was a 70-80% decrease in aromatase and estrogen levels in the neurons of these brain regions. The other bottom line: "Knockout mice can not remember as well as normal mice," says Brann.

They subjected male and female mice to extensive behavioral tests. They included mice whose ovaries were also removed as a control, to ensure that no circulating estrogen is found in the brain.

Electrophysiological studies performed on estrogen-altered brain slices have shown that although long-term potentiation – the process by which synapses strengthen to form a memory – worked, it did not function to the same degree. But putting an equivalent estrogen directly on the slices of the hippocampus helped restore that ability in a matter of minutes.

Inhibition of aromatase also decreased the expression of CREB, a major transcription factor that plays a key role in learning and memory, as well as neurotrophic factor derived from the brain and nourishing neurons (BDNF).

Despite the cognitive defects, the scientists only observed behavior similar to that of depression in animals without ovaries, and the levels of movement and anxiety were normal in all mice.

Scientists explain that these findings imply that estrogen derived neurons are a new neuromodulator, an essential messenger on which a neuron sustains to communicate with others, which is essential for key functions such as cognition.

"It's a direct genetic evidence of that role and I think it's important," Brann said.

Neuromodulators need to be created and released quickly, says Brann, who explains how estrogen is produced in the brain. We all have basal levels that can be quickly induced when needed, he adds.

It's probably the most abundant excitatory neurotransmitter glutamate in the brain, essential for learning and memory, which encourages neurons to produce estrogen, Brann adds.

Meanwhile, astrocytes, another type of brain cell that nourishes and nourishes neurons, seem to produce only estrogen in response to an injury. In this scenario, it is likely that cytokines, substances secreted by immune cells, also contribute to the action, prompting favorable astrocytes to start production, say scientists who have another project specifically focused on astrocytes.

Scientists are currently creating a double knockout, where aromatase is depleted in both neurons and astrocytes, since the well-being of these two types of brain cells is linked. Interestingly, the production of estrogen from the neuron may decrease in response to injury while the production of astrocyte increases. Brann notes that this seems to be another way, astrocytes protect neurons.

There are many empty areas left to fill before the natural process is understood in order to explore the potential for treatment, he says. This includes learning more about what regulates cerebral aromatase, whether estrogen levels decrease with normal aging and, if so, what could be used to increase aromatase and estrogen production in the body. the brain, explains Brann.

Estrogens, presumably produced by the ovaries, have long been considered to protect premenopausal women from cardiovascular disease, including stroke.

Brain estrogens also seem to benefit women because, although memory deficits occur in both sexes when their production is impaired, deficits are higher in women, Brann notes.

The ovaries also use aromatase, although its form is slightly different, to convert testosterone to estrogen. To date, evidence, including the new study, indicates that elimination of the ovaries does not affect estrogen levels in the brain, suggesting that the One does not depend on the other, explains Brann.

An enzyme that converts testosterone to estrogen plays an important role in the injured and healthy brain

More information:
Yujiao Lu et al. Estrogen derived from neurons regulate synaptic plasticity and memory, The journal of neuroscience (2019). DOI: 10.1523 / JNEUROSCI.1970-18.2019

Provided by
Georgia Medical College at Augusta University

Estrogen produced by important neurons for making memories (February 25, 2019)
recovered on February 25, 2019

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