GluA and GluN receptors regulate the surface density of GluN receptor subunits in cultured neocortical interneurons

Meyer, Dieter; Lindemeyer, A. Kerstin; Wilmes, Thomas; Sobottka, Helga; Nörenberg, Wolfgang

doi:10.1111/j.1471-4159.2012.07719.x

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…Fig. 2 C-F, when specified, neurons were incubated with an antibody binding to GluN1 extracellular domain (MAB363, Millipore); we note that this antibody allows for live labeling of surface NMDARs (43,44) for 60 min in normal culture media (10 μg/mL). Neurons were then washed once in culture media then incubated for 30-60 min with a secondary antibody (10 μg/mL; GAM-AF647, Life Technologies); both incubations were carried out at 37°C in the incubator.…”

Section: Methodsmentioning

confidence: 99%

Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow

Doré

Aow

Malinow

2015

Proc. Natl. Acad. Sci. U.S.A.

121

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The NMDA receptor (R) plays important roles in brain physiology and pathology as an ion channel. Here we examine the ion flowindependent coupling of agonist to the NMDAR cytoplasmic domain (cd). We measure FRET between fluorescently tagged cytoplasmic domains of GluN1 subunits of NMDARs expressed in neurons. Different neuronal compartments display varying levels of FRET, consistent with different NMDARcd conformations. Agonist binding drives a rapid and transient ion flow-independent reduction in FRET between GluN1 subunits within individual NMDARs. Intracellular infusion of an antibody targeting the GluN1 cytoplasmic domain blocks agonistdriven FRET changes in the absence of ion flow, supporting agonistdriven movement of the NMDARcd. These studies indicate that extracellular ligand binding to the NMDAR can transmit conformational information into the cell in the absence of ion flow.

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Section: Methodsmentioning

confidence: 99%

Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow

Doré

Aow

Malinow

2015

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

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“…The reduction in network bursts is due to changes in presynaptic activity which cause a pronounced decrease in glutamate release (Cohen and Segal 2009). It is tempting to hypothesize that the decrease in GluN receptor density observed in our experiments was caused by a lack of stimulation brought about by chronic application of NMDA (see the accompanying paper by D. K. Meyer et al 2012).…”

Section: Discussionmentioning

confidence: 83%

Stimulation of GluN receptors decreases the surface density of GluN1/GluN2B subunits in cultured neocortical interneurons

Nörenberg

Lindemeyer

Wilmes

et al. 2012

Journal of Neurochemistry

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J. Neurochem. (2012) 121, 587–596. Abstract Changes in the density of NMDA (GluN) receptors in the neuronal membrane are critical for plasticity, whereas malfunction of precisely regulated GluN receptor activity may be involved in neurotoxicity. In cultured rat neocortical interneurons, we have studied the regulation of the surface density of GluN1, GluN2A and GluN2B subunits. Application of 5 μMol NMDA for 24 h followed by a washout period of 24 h decreased the response of GluN receptors for at least 2 days. The reduction was caused by a decrease in the surface density of GluN1/GluN2B subunits, whereas GluN2A subunits remained unaffected. Our data indicate that long but reversible low level activation of GluN receptors can cause long‐term changes in their subunit composition in cultured interneurons.

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“…In this study, we found CMS-induced decrease in the intercommunicating molecules between neuron and microglia (Cx3cl1 / Cx3cr1 and CD200 / CD200R) in hippocampus of CMS-exposed mice was reversed by ASA VI treatment. Meanwhile, the PSD-95, CamKII α and CamKII β as well as decreased levels of phosphorylated GluA 2 in hippocampus of CMS-exposed mice, these are thought to be crucial for morphological maturation and synaptic development of hippocampal neurons [42][43][44][45][46][47], were partially reversed by asperosaponin VI via PPAR-γ-dependent pathway. These results reveal for the rst time the role of asperosaponin VI in maintaining normal communication between neurons and microglia as well as in repairing CMS-induced damage to synaptic plasticity in hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Asperosaponin VI Ameliorates The CMS-Induced Depressive-Like Behaviors By Inducing A Neuroprotective Microglial Phenotype To Restore Hippocampal Synaptic Plasticity Via PPAR-γ Pathway

Jiang

Liu

et al. 2021

Preprint

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Background: The natural compound asperosaponin VI has shown potential as an antidepressant, but how it works is unclear. Here we explored its effects on mice exposed to chronic mild stress (CMS) and the underlying molecular pathways.Methods: Mice were exposed to CMS for three weeks followed by asperosaponin VI (40 mg/kg) or imipramine (20 mg/kg) for another three weeks. Depression-like behaviors were assessed in the forced swimming test, sucrose preference test, tail suspension test, open field test and novelty-suppressed feeding test. Microglial phenotype and synaptic plasticity were evaluated using immunofluorescence staining, real-time quantitative PCR and enzyme-linked immunosorbent assays in hippocampus of mice. In some experiments, stressed animals were treated with the PPAR-γ antagonist GW9622 to examine its involvement in the effects of asperosaponin VI.Results: Asperosaponin VI ameliorated depression-like behaviors of CMS mice based on all three behavioral tests, and this was associated with a switch of hippocampal microglia from a pro-inflammatory (iNOS+-Iba1+) to neuroprotective (Arg-1+-Iba1+) phenotype. The natural compound also promoted interactions between hippocampal microglia and neurons by enhancing CX3CL1/CX3CR1 and CD200/CD200R, and preserved synaptic plasticity based on PSD95 and CamKIIa levels. These effects of asperosaponin VI were blocked by GW9662. Conclusion: CMS in mice induces a proinflammatory microglial phenotype, disrupting neuron-microglia communication and synaptic function in hippocampus, ultimately leading to depression-like behaviors. Asperosaponin VI may ameliorate the effects of CMS by inducing microglia to adopt a PPAR-γ-dependent neuroprotective phenotype.

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GluA and GluN receptors regulate the surface density of GluN receptor subunits in cultured neocortical interneurons

Cited by 4 publications

References 42 publications

Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow

Agonist binding to the NMDA receptor drives movement of its cytoplasmic domain without ion flow

Stimulation of GluN receptors decreases the surface density of GluN1/GluN2B subunits in cultured neocortical interneurons

Asperosaponin VI Ameliorates The CMS-Induced Depressive-Like Behaviors By Inducing A Neuroprotective Microglial Phenotype To Restore Hippocampal Synaptic Plasticity Via PPAR-γ Pathway

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