Neurosteroids Mediate Neuroprotection in an In Vitro Model of Hypoxic/Hypoglycaemic Excitotoxicity via δ-GABA$_{A}$ Receptors without Affecting Synaptic Plasticity

Puig-Bosch, Xènia; Ballmann, Markus; Bieletzki, Stefan; Antkowiak, Bernd; Rudolph, Uwe; Zeilhofer, Hanns Ulrich; Rammes, Gerhard

doi:10.3390/ijms24109056

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Puig-Bosch, X., Ballmann, M., Bieletzki, S., Antkowiak, B., Rudolph, U., Zeilhofer, H. U., & Rammes, G. (2023). Neurosteroids Mediate Neuroprotection in an In Vitro Model of Hypoxic/Hypoglycaemic Excitotoxicity via δ-GABA$_{A}$ Receptors without Affecting Synaptic Plasticity. International Journal of Molecular Sciences, 24(10), 9056. https://doi.org/10.3390/ijms24109056

Abstract

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), s