Woman looking up by Tachina Lee
Memory is a complex array of brain tissue working together to react to previously experienced situations. Scientists have long been delving into deeper and deeper territory in hopes to explain the mechanism in clear details. Thus far neurons have been identified as having reactions to a subset of situations through connections and their repeated use can explain memory consolidation. When a neuron is used often the connections are thought to strengthen through receptor mediated back talk namely through the NMDA receptor. As it turns out however, while these receptors do predominantly influence the synaptic plasticity, the ability to strengthen or weaken neuron connections, there seems to be another neurotransmitter at play.
Estrogen in commonly known as the female sex hormone which is derived from conversion of testosterone, the male sex hormone, using the enzyme aromatase. Lu and colleagues find that while estrogen can be found throughout both the male and female body, neurons seem to generate their own estrogen for their own purpose. This is because the neurons produce aromatase, the enzyme commonly found in female reproductive organs. Using a mouse model without the specific gene for forebrain aromatase, known as the forebrain aromatase knock-out (ARO-KO), they hope to compare it with normal mouse functions and neuronal contents to see if the change impacts memory and cognitive function.
Lu et. Al. use a variety of well known tests on the ARO-KO mice to test their mental processes and memory. They use the Barnes maze test to observe spatial memory which makes use of a safe room at the end of the maze which is removed after a few trials. If the mouse can not only locate the space where the safe room was but also spends an amount of time in the vacant space after the intial trials, the assumption is they did in fact remember properly. The other tests use similar schemes and assumptions to test their memory of previous experiences. These include novel object, forced swimming, open field, and fear conditioning tests all of which follow regulated guidelines and do not harm the subject more than needed. They find that with the aromatase knock-out the mice perform worse on these tests across the board such as in male mice, intact female mice, and ovariectomized female mice.
These findings show that the mice were in fact impacted negatively by the genetic knock-out procedure. However to ensure that these results occur on account of the lack of aromatase and therefore lack of estrogen in neuronal cells, they measure the amount estrogen in the brain specific regions they aim to affect. They also measured membrane excitatory potentials, the waves of neuron signals when given enough exciting neurotransmitter signals, and amount of neurotransmitter signal coming from the previous neuron. In this way they can see if less estrogen was produced due to the lack of aromatase and if that actually caused the weaker signalling or less strengthening of the neuron signals.
According to the research performed, Lu et. Al. discover that the aromatase knock-out inhibits proper memory formation and cognition. The tests show their impairment while the identification of presence of estrogen and aromatase show the procedure did what was intended. Their study also includes an identifying test whereby the affected knock-out mice are then dosed with estrogen as needed in these brain regions. They find that by then treating the estrogen deficient ARO-KO mice with estrogen, the mice are able to form memories properly once more. As such, using the collected data it can be safely assumed that neuronal derived estrogen has a strong influence on memory formation and consolidation, as well as cognition and decision making. This knowledge can be used to better understand how our brain works an more specifically how memory functions. They then go on to solidify their study while also implying a field of treatment using estrogen treatment. This may prove useful in future treatments of memory loss and relevant disorders.
In Depth
The study conducts extensive and near exhaustive experiments to identify the role of estrogen in memory and cognition. It takes the first step in this area and as such requires further followup. In particular it opens up discussion on this influence in humans and whether or not there are direct parallels to the dynamic found in mice. It is also important to uncover the underlying mechanism that estrogen might act through as a new receptor type or class may arise. This may also simply complicate function of an already discovered receptor, in which case more studies would be needed in that respect. Overall the study performs extensive research to properly cover all possible explanations. Figures can be better elucidated and integrated into the paper to streamline the reading process. This and other formatting issues can be overlooked as the current form of the paper that is out is barely a submitted manuscript.
Lu, Yujiao, Sareddy, Gangadhara R., Wang, Jing, et. Al. Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory. Journal of Neuroscience 6 February 2019, 1970-18; DOI: 10.1523/JNEUROSCI.1970-18.2019 http://www.jneurosci.org/content/early/2019/02/06/JNEUROSCI.1970-18.2019.abstract
Li, Fei and Joe Z Tsien. “Memory and the NMDA receptors” New England journal of medicine vol. 361,3 (2009): 302-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703758/
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