An antidepressant mechanism underlying the allosteric inhibition of GluN2D-incorporated NMDA receptors at GABAergic interneurons.

-methyl-d-aspartate receptors (NMDARs), key excitatory ion channels, have gained attention as anti-depression targets. NMDARs consist of two GluN1 and two GluN2 subunits (2A-2D), which determine their pharmacological properties. Few compounds selectively targeting GluN2 subunits with antidepressant effects have been identified.

GABAergic Progenitor Cell Graft Rescues Cognitive Deficits in Fragile X Syndrome Mice.

Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1-KO mice, MGE-derived cells from wild-type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons.

New monoamine antidepressant, hypidone hydrochloride (YL-0919), enhances the excitability of medial prefrontal cortex in mice via a neural disinhibition mechanism.

Hypidone hydrochloride (YL-0919) is a novel antidepressant in clinical phase II trial. Previous studies show that YL-0919 is a selective 5-HT (serotonin) reuptake inhibitor, 5-HT receptor partial agonist, and 5-HT receptor agonist, which exerts antidepressant effects in various animal models, but its effects on neural function remain unclear. Medial prefrontal cortex (mPFC), a highly evolved brain region, controls highest order cognitive functions and emotion regulation.

Ketamine activated glutamatergic neurotransmission by GABAergic disinhibition in the medial prefrontal cortex.

The fast-onset antidepressant actions of ketamine at subanaesthetic doses have attracted enormous interest in psychiatric disease treatment. However, the severe psychotomimetic side effects foster an urgent need to deeply understand the fast-onset antidepressant mechanism of ketamine. Ketamine, as a non-competitive NMDAR antagonist, increases the overall excitability of the mPFC, which is presumed to be essential for the antidepressant action of ketamine.

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

Rationale: Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties.

Objectives: The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD.

Methods: Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD.