Topic: N-methyl-D-aspartate receptor

Ketamine, an open-channel blocker of the N-methyl-D-aspartate receptor (NMDAR), has been shown to have rapid and sustained antidepressant effects after a single sub-anesthetic dose. Among its two enantiomers, (S)-ketamine acts more potently at NMDARs than (R)-ketamine, and its use as an antidepressant was approved by the FDA in 2019. Given that the mechanism underlying ketamine’s sustained antidepressant action remains unclear, we investigated if (S)-ketamine has any long-term effect on NMDAR-mediated synaptic transmission. In extracellular recordings from the CA1 region of mouse hippocampal s

N-Methyl-D-Aspartate receptor (NMDAR) encephalitis is a neurological disorder mediated by autoantibodies targeting the NMDAR. Patients’ autoantibodies are pathogenic, as they cause neuronal dysfunction in vitro, and molecular and behavioral changes in mouse models of cerebroventricular transfer of patients’ antibodies. Active immunization models have confirmed these effects and informed on the development of adaptive immune responses. Here we aimed to characterize the accompanying innate immune response and how this contributes to disease pathogenesis. Female C57BL/6 mice were immunized with N

GRIN disorders are rare neurodevelopmental disorders caused by pathogenic variants in the GRIN genes that encode the N-methyl-D-aspartate receptor (NMDAR) subunits. Two such missense variants of the GluN1 subunit, GRIN1-G620R and GRIN1-G827R, have been identified in multiple patients with profound intellectual disability and developmental delay. To understand the nature of the NMDAR deficits imparted by these variants, we generated Grin1 G620R and G827R mouse models that mimic the heterozygous condition found in affected individuals. Synaptic function was assessed using electrophysiological re

The dentate gyrus (DG) serves as an information gateway to the hippocampal formation. It receives sensory information from entorhinal cortex via perforant path (PP) and can be subdivided into parts including a supra- and an infrapyramidal blade. Typically, synaptic plasticity within the DG has mostly been examined in the suprapyramidal blade, whereas little is known about the extent to which synaptic plasticity is expressed and maintained in the infrapyramidal blade.This study compared synaptic plasticity in both blades of the DG that was evoked by patterned electrophysiological stimulation of

In human, genetic predispositions or deleterious environmental conditions may cause adverse effects on the developing brain. In preterm neonates, oligodendrocytes are particularly vulnerable and hypoxic conditions may result in white matter lesions leading to cerebral palsy and long-term disabilities. The glutamatergic transmission plays a critical role in the pathophysiology of these lesions but it is also a key actor involved in developmental mechanisms such as cell differentiation. Previous studies demonstrated a strong expression of the N-methyl-D-aspartate receptor by endothelial cells (e

N-methyl-D-aspartate receptor (NMDAR) is a glutamate-gated ion channel permeable to calcium that plays critical roles in synaptic transmission, synaptogenesis, and plasticity. Recent sequencing data in neurological and psychiatric patients reveal numerous variants in genes encoding NMDAR subunits. In our study, we have created and evaluated a transgenic mouse line carrying a frameshift variant (Grin2b L825FfsX4) resulting in the deletion of about half of the GluN2B subunit. Our methods included patch-clamp recordings from hippocampal neurons in both wild-type (Grin2bWT/WT) and transgenic (Grin

Spinocerebellar ataxias (SCA) are a group of inherited neurodegenerative diseases. The most common SCAs are caused by an expansion of the trinucleotide CAG, which produces a polyglutamine tract in their encoded proteins, leading to their aggregation. Patients suffering from these disorders display movement impairments, and no effective treatment exists, leading to death 10-15 years after disease onset. Until now, nearly all attempts to use traditional N-methyl-d-aspartate receptor (NMDAR) antagonists to treat neurodegenerative diseases have failed. This is because NMDARs are not only promoters

Autoantibodies (aAb) against N-methyl-D-aspartate receptor (NMDAR) mediate autoimmune Anti-NMDAR encephalitis. This leads to the development of various symptoms, including seizures, memory deficits, cognitive dysfunction, and psychosis. Our current understanding of the pathophysiology remains limited. Particularly the crucial molecular insights of autoantibody recognition and the influence of their binding on the function of NMDARs. To address these knowledge gaps, we characterized three patient-derived monoclonal antibodies in a multi-modal approach, encompassing super-resolution microscopy,