Evidence map›Paper›PMID 33803741›Full record

ArticleInternational journal of molecular sciences2021

De novo Neurosteroidogenesis in Human Microglia: Involvement of the 18 kDa Translocator Protein.

Lorenzo Germelli, Eleonora Da Pozzo, Chiara Giacomelli, Chiara Tremolanti, Laura Marchetti, Christian H Wetzel, Elisabetta Barresi, Sabrina Taliani, Federico Da Settimo, Claudia Martini and 1 more

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. The Effects of Neuroactive Steroids on Myelin in Health and Disease.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2024
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Autism-Like Behavior in the Offspring ofFrontiers in neuroscience · 2021
    Article
  18. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Lorenzo GermelliDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-7318-7545
Eleonora Da PozzoDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0003-4762-8949
Chiara GiacomelliDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-6244-602X
Chiara TremolantiDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-3113-7099
Laura MarchettiDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.
Christian H WetzelDepartment of Psychiatry and Psychotherapy, Molecular Neurosciences, University of Regensburg, 93053 Regensburg, Germany.ORCID 0000-0002-5762-0003
Elisabetta BarresiDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-9814-7195
Sabrina TalianiDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0001-8675-939X
Federico Da SettimoDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0002-7897-7917
Claudia MartiniDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.ORCID 0000-0001-9379-3027
Barbara CostaDepartment of Pharmacy, University of Pisa, 56126 Pisa, Italy.
University of Pisa · ITUniversity of Regensburg · DE

Funding

Italian Ministry of Education, Universities and Research 2017MT3993
6 · The paper itself

Abstract

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. Unexpectedly, immortalized murine microglia recently exhibited this de novo biosynthesis; herein, de novo neurosteroidogenesis was characterized in immortalized human microglia. The results demonstrated that C20 and HMC3 microglial cells constitutively express members of the neurosteroidogenesis multiprotein machinery-in particular, the transduceosome members StAR and TSPO, and the enzyme CYP11A1. Moreover, both cell lines produce pregnenolone and transcriptionally express the enzymes involved in neurosteroidogenesis. The high TSPO expression levels observed in microglia prompted us to assess its role in de novo neurosteroidogenesis. TSPO siRNA and TSPO synthetic ligand treatments were used to reduce and prompt TSPO function, respectively. The TSPO expression downregulation compromised the de novo neurosteroidogenesis and led to an increase in StAR expression, probably as a compensatory mechanism. The pharmacological TSPO stimulation the de novo neurosteroidogenesis improved in turn the neurosteroid-mediated release of Brain-Derived Neurotrophic Factor. In conclusion, these results demonstrated that de novo neurosteroidogenesis occurs in human microglia, unravelling a new mechanism potentially useful for future therapeutic purposes.

Indexed as

Brain-Derived Neurotrophic FactorCell LineGene Expression RegulationHumansMicrogliaNeurosteroidsPregnenoloneReceptors, GABABrain-Derived Neurotrophic FactorNeurosteroidsPregnenoloneReceptors, GABATSPO protein, human18 kDa TSPOBDNFCYP11A1human microglial cellsneurosteroidogenesisneurosteroidsStAR proteinTSPO ligands

Identifiers

PMID33803741
PMCPMC8003294
OpenAlexW3139329113

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.