更新于：2024-11-01

GluN1 x GRIN3A

更新于：2024-11-01

基本信息

关联

项与 GluN1 x GRIN3A 相关的药物

WZB117(Inhibitor of GluN1/GluN3 NMDA Receptors)

靶点

GRIN3A x GluN1

作用机制

GRIN3A antagonists [+1]

在研机构

中国科学院上海药物研究所

原研机构

中国科学院上海药物研究所

在研适应症

神经系统疾病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 GluN1 x GRIN3A 相关的临床结果

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100 项与 GluN1 x GRIN3A 相关的转化医学

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0 项与 GluN1 x GRIN3A 相关的专利（医药）

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项与 GluN1 x GRIN3A 相关的文献（医药）

2024-10-16·The Journal of Neuroscience

GluN3A and Excitatory Glycine Receptors in the Adult Hippocampus

Article

作者: Fang, Lisa Z ; Parsons, Matthew P ; Hirasawa, Michiru ; Nafar, Firoozeh ; Mukherjee, Bandhan ; Hurley, Emily P ; Barnes, Jocelyn R ; Barron, Jessica C

The GluN3A subunit ofN-methyl-D-aspartate receptors (NMDARs) plays an established role in synapse development, but its contribution to neural circuits in the adult brain is less clear. Recent work has demonstrated that in select cell populations, GluN3A assembles with GluN1 to form GluN1/GluN3A receptors that are insensitive to glutamate and instead serve as functional excitatory glycine receptors (eGlyRs). Our understanding of these eGlyRs, and how they contribute to intrinsic excitability and synaptic communication within relevant networks of the developing and the mature brain, is only beginning to be uncovered. Here, using male and female mice, we demonstrate that GluN3A subunits are enriched in the adult ventral hippocampus (VH), where they localize to synaptic and extrasynaptic sites and can assemble as functional eGlyRs on CA1 pyramidal cells. GluN3A expression was barely detectable in the adult dorsal hippocampus (DH). We also observed a high GluN2B content in the adult VH, characterized by slow NMDAR current decay kinetics and a high sensitivity to the GluN2B-containing NMDAR antagonist ifenprodil. Interestingly, the GluN2B enrichment in the adult VH was dependent on GluN3A as GluN3A deletion accelerated NMDAR decay and reduced ifenprodil sensitivity in the VH, suggesting that GluN3A expression can regulate the balance of conventional NMDAR subunit composition at synaptic sites. Lastly, we found that GluN3A knock-out also enhanced both NMDAR-dependent calcium influx and NMDAR-dependent long-term potentiation in the VH. Together, these data reveal a novel role for GluN3A and eGlyRs in the control of ventral hippocampal circuits in the mature brain.

2024-07-31·The FASEB Journal

Interplay of miRNAs and molecular pathways in spaceflight‐induced depression: Insights from a rat model using simulated complex space environment

Article

作者: Rasheed, Madiha ; Maazouzi, Mohamed ; Deng, Yulin ; Chen, Zixuan ; Wang, Han ; Li, Yumeng ; Tahir, Rana Adnan

AbstractDepression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight‐induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space‐induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR‐455‐3p, miR‐206‐3p, miR‐132‐3p, miR‐16‐5p, miR‐124‐3p, and miR‐145‐3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight‐induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT‐PCR and HPLC, respectively. Results showed that SCSE‐exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR‐455‐3p, miR‐206‐3p, miR‐132‐3p, and miR‐16‐5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight‐induced depression. Protein–protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR‐455‐3p and miR‐206‐3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.

2024-04-12·Science Advances

Structure and function of GluN1-3A NMDA receptor excitatory glycine receptor channel

Article

作者: Michalski, Kevin ; Furukawa, Hiro