Germelli, Lorenzo and Da Pozzo, Eleonora and Giacomelli, Chiara and Tremolanti, Chiara and Marchetti, Laura and Wetzel, Christian H. and Barresi, Elisabetta and Taliani, Sabrina and Da Settimo, Federico and Martini, Claudia and Costa, Barbara (2021) De novo Neurosteroidogenesis in Human Microglia: Involvement of the 18 kDa Translocator Protein. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (6): 3115. ISSN 1422-0067
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MACROPHAGES; PHENOTYPES; EXPRESSION; LIGANDS; 18 kDa TSPO; human microglial cells; neurosteroidogenesis; neurosteroids; StAR protein; BDNF; TSPO ligands |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie > Molekulare Neurowissenscahften |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Aug 2022 04:36 |
| Last Modified: | 26 Aug 2022 04:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46918 |
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