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Interesting article in @CellCellPress re #COVID, sex hormones, and GABA
Sex and COVID-19: A Protective Role for Reproductive Steroids
https://www.cell.com/action/showPdf?pii=S1043-2760%2820%2930222-8
@VirusesImmunity @ShelFarFar @ericsongg
Sex and COVID-19: A Protective Role for Reproductive Steroids
https://www.cell.com/action/showPdf?pii=S1043-2760%2820%2930222-8
@VirusesImmunity @ShelFarFar @ericsongg
2/ Interestingly, the article brings up Allopregnanolone, an endogenous inhibitory pregnane neurosteroid. It is made from progesterone, and is a positive allosteric modulator of the action of γ-aminobutyric acid (GABA) at GABAA receptor.
3/ You may have heard of brexanolone (Zulresso) the drug specifically made for postpartum depression, costing approximately $34,000 per patient for a course of treatment that must be infused over 60 hours under medical supervision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf
4/ This drug was only just approved by the FDA in March 2019. Brexanolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator, that is chemically identical to endogenous allopregnanolone @jackie_parchem @janevandis https://www.washingtonpost.com/health/2019/03/19/first-drug-specifically-postpartum-depression-is-approved/
5/ This is interesting because in pregnancy, the increase in plasma progesterone triggers upregulation of allopregnanolone levels, which reaches the highest blood concentrations during the 3rd trimester. Following childbirth, these neurohormones abruptly decrease.
6/ The expression of specific subunits of the GABA-A receptor coordinate with fluctuations in neurosteroid concentrations during both pregnancy & the menstrual cycle. https://www.frontiersin.org/articles/10.3389/fendo.2020.00236/full#B36
7/ Changes to the GABA-A receptor structure, function, or its expression can cause disruption to cognitive functions, mood, and emotions. And GABAergic neuron activation within the hypothalamus is modulated by the hypothalamic-pituitary-adrenal (HPA) axis.
8/ Allopregnanolone also inhibits HPA axis activity & represses stress elevation of ACTH and corticosterone. As @graziano_pinna states in both above articles, the neurobiology of mood disorders remains understudied. @drjessigold
9/ Certain drugs called 5‐alpha reductase inhibitors have antiandrogenic effects (including finasteride), which result in a decrease of allopregnanolone & can affect expression of GABA-A receptor. This is interesting in light of this other recent paper: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30547-6
10/ Again, why do I care? Because of the potential cross over between neurological sx, pre-existing immune dysregulation, disrupted baseline neurotransmitter function in addition to the impact of sex hormones...and the effect this has on who develops & the severity of #COVID19
If you are curious, please check out:
THREAD: GABA, Neuro- #COVID, & the Immune System
https://twitter.com/ErinSandersNP/status/1315210076785909760?s=20
THREAD: More GABA data from anesthesia!
https://twitter.com/ErinSandersNP/status/1315610019291955200?s=20
THREAD: I’m obsessed with the eyes, brains, GABA, autopsies & #COVID19 https://twitter.com/ErinSandersNP/status/1320250579482980355?s=20
THREAD: GABA, Neuro- #COVID, & the Immune System
https://twitter.com/ErinSandersNP/status/1315210076785909760?s=20
THREAD: More GABA data from anesthesia!
https://twitter.com/ErinSandersNP/status/1315610019291955200?s=20
THREAD: I’m obsessed with the eyes, brains, GABA, autopsies & #COVID19 https://twitter.com/ErinSandersNP/status/1320250579482980355?s=20
