Neurons in both males and females make estrogen. But, when they don’t, their brains have significantly less dense spines and synapses. Now, a new study suggests that the estrogen is essential to keep neurons communicating and memories being made.
Darrell Brann, interim chair of the Department of Neuroscience and Regenerative Medicine at the Medical College of Georgia at Augusta University said, “We think this shows estrogen has a clear role in synaptic plasticity, how the neurons communicate and in memory.”
Scientists found that mice whose neurons don’t influence estrogen to have debilitated spatial reference memory – like a baseball player not realizing where home plate is and getting there – just as acknowledgment memory and contextual fear memory – so they experience difficulty remembering what’s hazardous. Restoring estrogen levels to the brain area rescues these impaired functions.
Brann said, “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 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.”
For the study, scientists knocked aromatase out of the forebrain, which includes the hippocampus, which has a role in making long-term memories and spatial memory, and the cerebral cortex, which is important to memory, attention, awareness and thought. They depleted aromatase only in the excitatory neurons – called excitatory because they help make some action like a thought happen – in the forebrain as a way to focus on the role of estrogen produced by these brain cells.
Brann said, “The bottom line was a 70-80 percent 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.”
They put male and female mice through broad behavioral testing. They included mice that additionally had their ovaries evacuated as a control, to guarantee that no circulating estrogen wound up in the brain.
Electrophysiological investigations of cuts of the estrogen-altered brain demonstrated that while long haul potentiation – which is the procedure by which synapses strengthen to form a memory – worked, it didn’t the capacity to about a similar degree. Yet, putting a proportional estrogen directly onto cuts of the hippocampus reestablished that capacity inside minutes.
Knocking out aromatase likewise diminished articulation of CREB, a noteworthy translation factor known to assume a key job in learning and memory, the researchers compose, just as neuron-feeding mind determined neurotrophic factor or BDNF.
Despite the cognitive defects, the scientists only saw depression-like behavior in the animals with their ovaries removed, and movement and anxiety levels were normal in all the mice.
The scientists said, “The findings implicate neuron-derived estrogen as a novel neuromodulator, basically a critical messenger one neuron relies on to communicate with others, which is essential to key functions like cognition.”
Brann said, “It’s direct genetic evidence of this role and I think that is important to have. Neuromodulators need to be created and released quickly, Brann says, which is how estrogen gets produced in the brain. We all have basal levels that can be rapidly induced when needed.”
“It’s likely glutamate, the brain’s most abundant excitatory neurotransmitter, which is essential to learning and memory, that prompts the neurons’ production of estrogen.”
Means astrocytes only seem to make estrogen in response to injury. In that case, it’s likely cytokines, substances secreted by immune cells to also make something happen, that prompt supportive astrocyte to start production.
The scientists are now creating double knockouts, where aromatase is depleted in both neurons and astrocytes since the wellbeing of these two brain cell types is connected. Interestingly, the neuron’s estrogen production may drop in response to injury while the astrocyte’s production steps up.
Brann said, “There are many blanks left to fill in before the natural process will be understood so treatment potential could be explored. 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.”
“Estrogen, presumably produced by the ovaries, has long been considered to protect premenopausal women from cardiovascular disease, including stroke.”
“Brain estrogen also appears to give a bit of an edge to females because, while memory deficits occurred in both sexes when its production was impaired, deficits were more significant in the females.”
“The ovaries also use aromatase, although a slightly different form, to convert testosterone to estrogen. Evidence to date, including the new study, indicate that removing the ovaries does not impact brain levels of estrogen, suggesting that one is not dependent on the other.”
The study is published in the J Neurosci- The Journal of Neuroscience.