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The Neuroactive Steroid Pregnanolone Glutamate: Anticonvulsant Effect, Metabolites and Its Effect on Neurosteroid Levels in Developing Rat Brains

2021-12 Kudova E, Mares P, Hill M, Vondrakova K, Tsenov G, Chodounska H, Kubova H, Vales K

Pregnanolone glutamate (PA-G) is a neuroactive steroid that has been previously demonstrated to be a potent neuroprotective compound in several biological models in vivo. Our in vitro experiments identified PA-G as an inhibitor of N-methyl-D-aspartate receptors and a potentiator of γ-aminobutyric acid receptors (GABAARs).

Circadian rhythms of 11-oxygenated C19 steroids and ∆5-steroid sulfates in healthy men

2021-08 Turcu AF, Zhao L, Chen X, Yang R, Rege J, Rainey WE, Veldhuis JD, Auchus RJ

Many hormones display distinct circadian rhythms, driven by central regulators, hormonal bioavailability, and half-life. A set of 11-oxygenated C19 steroids (11-oxyandrogens) and pregnenolone sulfate (PregS) are elevated in congenital adrenal hyperplasia and other disorders, but their circadian patterns have not been characterized.

Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study

2021-03 Rustichelli C, Bellei E, Bergamini S, Monari E, Lo Castro F, Baraldi C, Tomasi A, Ferrari A

Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age.

De novo neurosteroidogenesis in human microglia: involvement of the 18 kDa translocator protein

2021-03 Germelli L, Da Pozzo E, Giacomelli C, Tremolanti C, Marchetti L, Wetzel CH, Barresi E, Taliani S, Da Settimo F, Martini C, Costa B

Neuroactive steroids are potent modulators of microglial functions and are capable of counteracting their excessive reactivity. This action has mainly been ascribed to neuroactive steroids released from other sources, as microglia have been defined unable to produce neurosteroids de novo.

Epigenetic regulation of GABAergic neurotransmission and neurosteroid biosynthesis in alcohol use disorder

2021-02 Gatta E, Guidotti A, Saudagar V, Grayson DR, Aspesi D, Pandey SC, Pinna G

Alcohol use disorder (AUD) is a chronic relapsing brain disorder. GABAA receptor (GABAAR) subunits are a target for the pharmacological effects of alcohol. Neurosteroids play an important role in the fine-tuning of GABAAR function in the brain. Recently, we have shown that AUD is associated with changes in DNA methylation mechanisms. However, the role of DNA methylation in the regulation of neurosteroid biosynthesis and GABAergic neurotransmission in AUD patients remains under-investigated.

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