ArticleScientific reports2019
Endogenous Neurosteroid (3α,5α)3-Hydroxypregnan-20-one Inhibits Toll-like-4 Receptor Activation and Pro-inflammatory Signaling in Macrophages and Brain.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 115 citations in OpenAlex.
- Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial.JAMA network open · 2020Trial
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Neurosteroid (3α,5α)3-hydroxypregnan-20-one enhancement of anti-inflammatory chemokine CX3CL1 exhibits sex, brain region, and cellular specificity in alcohol-preferring rats.Psychopharmacology · 2026Article
- Structure-activity relationships of steroid and sterol neuromodulators on inflammatory markers in a murine microglial cell line.The Journal of steroid biochemistry and molecular biology · 2026Article
- YY1 Transcriptionally Activates USP19 to Mediate TRAF6 Deubiquitination to Promote Microglial Inflammation and M1 Polarization in Depression Development.Neurochemical research · 2026Article
- Alterations in GABAergic Interneurons, Neuroinflammation, and Epigenetics: Potential Targets for Therapeutic Strategies in Schizophrenia.Current neuropharmacology · 2026Article
- Brexanolone infusion produces sustained anti-inflammatory and neurotrophic effects in patients with postpartum depression that predict symptom improvement.Translational psychiatry · 2026Article
- GABADrug design, development and therapy · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Serum steroid metabolome pattern is associated with the response to prednisolone therapy of male patients with IgA nephropathy.Renal failure · 2025Article
- Microglia alter sex-specific cerebellar myelination following placental hormone loss.Nature communications · 2025Article
- Unravelling the multifaceted actions of neurosteroids: Machine learning and in vitro screening for novel target discovery.British journal of pharmacology · 2025Article
- Sex Steroids in COVID-19 Patients with Hypertension: An Exploratory Study.International journal of molecular sciences · 2025Article
- Neurosteroids, Microbiota, and Neuroinflammation: Mechanistic Insights and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Neuroactive Steroids as Novel Promising Drugs in Therapy of Postpartum Depression-Focus on Zuranolone.International journal of molecular sciences · 2025Review
- Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution.Journal of neuroendocrinology · 2025Review
- Steroidomic Changes in the Cerebrospinal Fluid of Women with Multiple Sclerosis.International journal of molecular sciences · 2025Article
- From neurotoxicity to neuroprotection: Rethinking GABACell biology and toxicology · 2025Review
- Allopregnanolone Regulation of Phasic Dopamine Release and Motivated Behavior.ACS chemical neuroscience · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The endogenous neurosteroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) has protective activity in animal models of alcoholism, depression, traumatic brain injury, schizophrenia, multiple sclerosis, and Alzheimer's disease that is poorly understood. Because these conditions involve proinflammatory signaling through toll-like receptors (TLRs), we examined the effects of 3α,5α-THP, and pregnenolone on TLR4 activation in both the periphery and the central nervous system (CNS). We used monocytes/macrophages (RAW264.7) as a model of peripheral immune signaling and studied innately activated TLR4 in the ventral tegmental area (VTA) of selectively bred alcohol-preferring (P) rats. LPS activated the TLR4 pathway in RAW264.7 cells as evidenced by increased levels of p-TAK1, TRAF6, NF-κB p50, phospho-NF-κB- p65, pCREB, HMGB1, and inflammatory mediators, including MCP-1 and TNFα. Both 3α,5α-THP and pregnenolone (0.5-1.0μM) substantially (~80%) inhibited these effects, indicating pronounced inhibition of TLR4 signaling. The mechanism of inhibition appears to involve blockade of TLR4/MD-2 protein interactions in RAW246.7 cells. In VTA, 3α,5α-THP (15 mg/kg, IP) administration reduced TRAF6 (~20%), CRF (~30%), and MCP-1 (~20%) levels, as well as TLR4 binding to GABA
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.