Medical Studies on Pregnenolone

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).

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.

BV-2 microglial cells respond to rotenone toxic insult by modifying pregnenolone, 5α-dihydroprogesterone and pregnanolone levels

2020-09 Avallone R, Lucchi C, Puja G, Codeluppi A, Filaferro M, Vitale G, Rustichelli C, Biagini G

Neuroinflammation, whose distinctive sign is the activation of microglia, is supposed to play a key role in the development and progression of neurodegenerative diseases. The aim of this investigation was to determine levels of neurosteroids produced by resting and injured BV-2 microglial cells.

Site of action of brain neurosteroid pregnenolone sulfate at the N-Methyl-D-Aspartate Receptor

2020-07 Hrcka Krausova B, Kysilov B, Cerny J, Vyklicky V, Smejkalova T, Ladislav M, Balik A, Korinek M, Chodounska H, Kudova E, Vyklicky L

N-methyl-D-aspartate receptor (NMDAR) hypofunction has been implicated in several neurodevelopmental disorders. NMDAR function can be augmented by positive allosteric modulators, including endogenous compounds, such as cholesterol and neurosteroid pregnenolone sulfate (PES).

Stress and drug abuse-related disorders: the promising therapeutic value of neurosteroids focus on pregnenolone-progesterone-allopregnanolone pathway

2019-10 Tomaselli G , Vallée M

The pregnenolone-progesterone-allopregnanolone pathway is receiving increasing attention in research on the role of neurosteroids in pathophysiology, particularly in stress-related and drug use disorders. These disorders involve an allostatic change that may result from deficiencies in allostasis or adaptive responses, and may be downregulated by adjustments in neurotransmission by neurosteroids.

Neurosteroid levels in patients with bipolar disorder and a history of cannabis use disorders

2017-12 Van Enkevort E, Filbey F, Marx CE, Park J, Nakamura A, Sunderajan P, Brown ES

In animal models, levels of the neurosteroid pregnenolone increase after tetrahydrocannabinol (THC) administration and pregnenolone appears to attenuate the brain effects of THC. Given these interactions between pregnenolone and THC, we evaluated baseline neurosteroid levels in participants with a history of a cannabis use disorders (CUDs).

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