| First Author | Puig-Bosch X | Year | 2023 |
| Journal | Int J Mol Sci | Volume | 24 |
| Issue | 10 | PubMed ID | 37240402 |
| Mgi Jnum | J:336166 | Mgi Id | MGI:7487275 |
| Doi | 10.3390/ijms24109056 | Citation | Puig-Bosch X, et al. (2023) Neurosteroids Mediate Neuroprotection in an In Vitro Model of Hypoxic/Hypoglycaemic Excitotoxicity via delta-GABA(A) Receptors without Affecting Synaptic Plasticity. Int J Mol Sci 24(10) |
| abstractText | Neurosteroids and benzodiazepines are modulators of the GABA(A) receptors, thereby causing anxiolysis. Furthermore, benzodiazepines such as midazolam are known to cause adverse side-effects on cognition upon administration. We previously found that midazolam at nanomolar concentrations (10 nM) blocked long-term potentiation (LTP). Here, we aim to study the effect of neurosteroids and their synthesis using XBD173, which is a synthetic compound that promotes neurosteroidogenesis by binding to the translocator protein 18 kDa (TSPO), since they might provide anxiolytic activity with a favourable side-effect profile. By means of electrophysiological measurements and the use of mice with targeted genetic mutations, we revealed that XBD173, a selective ligand of the translocator protein 18 kDa (TSPO), induced neurosteroidogenesis. In addition, the exogenous application of potentially synthesised neurosteroids (THDOC and allopregnanolone) did not depress hippocampal CA1-LTP, the cellular correlate of learning and memory. This phenomenon was observed at the same concentrations that neurosteroids conferred neuroprotection in a model of ischaemia-induced hippocampal excitotoxicity. In conclusion, our results indicate that TSPO ligands are promising candidates for post-ischaemic recovery exerting neuroprotection, in contrast to midazolam, without detrimental effects on synaptic plasticity. |
