Some of the important findings from the work by Monsheel Sodhi et al. include concerns and research on the relationship between glutamate and suicide/psychological disorders. Compared to males, it was found that females have higher GluR (glutamate receptor) expression in suicides and an elevation in Glu transporters (in depressed women). Additionally, their research has implications that severe depression may be due to glutamate spillover.
The sex hormones and glutamate interaction subtopic in the article by Claudia Barth, Arno Villringer, and Julia Sacher emphasizes the importance of the integration of glutamatergic transmission for normal cognitive functioning and mental health. Through research with rodents, it was found that progesterone suppresses excitatory glutamate response in a dose-dependent fashion, while “estrogen exhibits facilitating effects on glutamate transmission” (Barth et al., 2015). Progesterone was found to have an impact on non-NMDA receptors the most, while estrogen effects cognition via NMDA glutamate receptors. Specifically, “estrogen has been shown to promote an increase in NMDA receptor subunit expression, binding sites, and neuronal sensitivity to synaptic input mediated by NMDA glutamate receptors” (Barth et al., 2015). The interaction between glutamate and estrogen impacts cognition (i.e. executive function and working memory), specifically under “harmful conditions” like stress. It was found that normal estrogen levels and signaling is necessary for the prefrontal cortex and hippocampus (the brain regions involved) to counter the impacts of harmful conditions.
According to Dr. Kate Placzek in “How Pill Contraceptives Affect Mood & Behavior,” estrogen and progesterone not only play a neuromodulatory role for complex biological processes, but they also play a “critical role in regulating cognition, learning, memory, emotion, mood, and motor control” (Placzek, 2016). This modulation can be a result of estrogen and progesterone directly acting on their receptors, or by interacting with dominant neurotransmitter systems (for this, we are mostly concerned with glutamate).
Now you might ask, why does all this matter? Although the underlying mechanism (the causation) has not been directly evaluated in these collection of studies, it is a possible concern that women who use some form of contraceptive medication or technology involving estrogen are at an increased risk for depression and suicide.
If we compile these various sources, then we should be able to make two statements, in which we will focus on estrogen and females: 1) If there is an increase in estrogen (due to some form of contraceptive), there is a promoted expression of a glutamate receptor called NMDA receptor (NMDAR). 2) There is an increase in glutamate receptor expression that was found in suicides (Sodhi et al., 2015). Therefore, a future direction for these studies would be to determine whether an increase in estrogen from certain contraceptives may result in an increased risk for depression and suicide.
Sources:
Barth, C., Villringer, A., & Sacher, J. (2015). Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods. Frontiers in neuroscience, 9, 37. doi:10.3389/fnins.2015.00037
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