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Differential depletion of GluN2A induces heterogeneous schizophrenia-related phenotypes in miceResearch in context

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العنوان: Differential depletion of GluN2A induces heterogeneous schizophrenia-related phenotypes in miceResearch in context
المؤلفون: Yi Lu, Longyu Mu, Justin Elstrott, Chaoying Fu, Cailu Sun, Tonghui Su, Xiaofan Ma, Jia Yan, Hong Jiang, Jesse E. Hanson, Yang Geng, Yelin Chen
المصدر: EBioMedicine, Vol 102, Iss , Pp 105045- (2024)
بيانات النشر: Elsevier, 2024.
سنة النشر: 2024
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: NMDA receptor, GluN2A, Schizophrenia, Conditional knockout mouse, Medial prefrontal cortex, Excitatory synaptic transmission, Medicine, Medicine (General), R5-920
الوصف: Summary: Background: Schizophrenia, a debilitating psychiatric disorder, displays considerable interindividual variation in clinical presentations. The ongoing debate revolves around whether this heterogeneity signifies a continuum of severity linked to a singular causative factor or a collection of distinct subtypes with unique origins. Within the realm of schizophrenia, the functional impairment of GluN2A, a subtype of the NMDA receptor, has been associated with an elevated risk. Despite GluN2A’s expression across various neuronal types throughout the brain, its specific contributions to schizophrenia and its involvement in particular cell types or brain regions remain unexplored. Methods: We generated age-specific, cell type-specific or brain region-specific conditional knockout mice targeting GluN2A and conducted a comprehensive analysis using tests measuring phenotypes relevant to schizophrenia. Findings: Through the induction of germline ablation of GluN2A, we observed the emergence of numerous schizophrenia-associated abnormalities in adult mice. Intriguingly, GluN2A knockout performed at different ages, in specific cell types and within distinct brain regions, we observed overlapping yet distinct schizophrenia-related phenotypes in mice. Interpretation: Our interpretation suggests that the dysfunction of GluN2A is sufficient to evoke heterogeneous manifestations associated with schizophrenia, indicating that GluN2A stands as a prominent risk factor and a potential therapeutic target for schizophrenia. Funding: This project received support from the Shanghai Municipal Science and Technology Major Project (Grant No. 2019SHZDZX02) awarded to Y.C. and the Natural Science Foundation of Shanghai (Grant No. 19ZR1468600 and 201409003800) awarded to G.Y.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S235239642400080X; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2024.105045
URL الوصول: https://doaj.org/article/cbaf650e8efe4b698fad41585b8367f6
رقم الأكسشن: edsdoj.baf650e8efe4b698fad41585b8367f6
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2024.105045