Neurosteroid Modulation of Synaptic and Extrasynaptic GABAA Receptors of the Mouse Nucleus Accumbens

Biomolecules, Journal Year: 2024, Volume and Issue: 14(4), P. 460 - 460

Published: April 9, 2024

The recent approval of formulations the endogenous neurosteroid allopregnanolone (brexanolone) and synthetic neuroactive steroid SAGE-217 (zuranolone) to treat postpartum depression (PPD) has encouraged further research elucidate why these potent enhancers GABAAR function are clinically effective in this condition. Dopaminergic projections from ventral tegmental area (VTA) nucleus accumbens associated with reward/motivation brain imaging studies report that individuals PPD show reduced activity pathway response reward infant engagement. However, influence neurosteroids on GABA-ergic transmission received limited attention. Here, we investigate, medium spiny neurons (MSNs) mouse core, effect allopregnanolone, other steroids interest fast phasic tonic inhibition mediated by synaptic (α1/2βγ2) extrasynaptic (α4βδ) GABAARs, respectively. We present evidence suggesting resident current results spontaneous opening δ-GABAARs, where steroid-enhanced is GABA-dependent. Furthermore, demonstrate local synthesis accumbal slice preparation reveal neurotransmission MSNs influenced an tone. Given dramatic fluctuations levels during pregnancy postpartum, neurosteroid-mediated fine-tuning GABAergic will probably be perturbed.

Language: Английский

DDL-920 mediated enhancement of γ-oscillations targeting γ-aminobutyric acid receptors: a novel therapeutic strategy to improve cognition in Alzheimer's disease

Neurology Letters, Journal Year: 2025, Volume and Issue: 4(1), P. 42 - 47

Published: March 16, 2025

Language: Английский