دورية أكاديمية
Brain region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice
| العنوان: | Brain region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice |
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| المؤلفون: | Farsi, Zohreh, Nicolella, Ally, Simmons, Sean, Aryal, Sameer, Shepard, Nate, Brenner, Kira, Lin, Sherry, Herzog, Linnea, Shin, Wangyong, Gazestani, Vahid, Song, Bryan, Bonanno, Kevin, Keshishian, Hasmik, Carr, Steven, Macosko, Evan, Datta, Sandeep, Dejanovic, Borislav, Kim, Eunjoon, Levin, Joshua, Sheng, Morgan |
| سنة النشر: | 2023 |
| المجموعة: | Zenodo |
| الوصف: | Schizophrenia disease mechanisms remain poorly understood, in large part due to a lack of valid animal models. Rare heterozygous loss-of-function mutations in GRIN2A, encoding a subunit of the NMDA (N-methyl-d-aspartate) receptor, greatly increase the risk of schizophrenia. By transcriptomic, proteomic, electroencephalogram (EEG) recording and behavioral analysis, we report that heterozygous Grin2a mutant mice show: (i) large-scale gene expression changes across multiple brain regions and in neuronal (excitatory and inhibitory) and non-neuronal cells (astrocytes, oligodendrocytes); (ii) evidence of reduced activity in prefrontal cortex and increased activity in hippocampus and striatum; (iii) elevated dopamine signaling in striatum; (iv) altered cholesterol biosynthesis in astrocytes; (v) reduction of glutamatergic receptor signalin g proteins in the synapse; (iv) heightened gamma oscillation power in EEG; (vi) aberrant locomotor behavioral pattern opposite of that induced by antipsychotic drugs. These findings reveal potential pathophysiologic mechanisms, provide support for both the “hypo-glutamate” and “hyper-dopamine” hypotheses of schizophrenia, and underscore the utility of Grin2a-deficient mice as a new genetic model of schizophrenia. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://zenodo.org/record/8145320Test; https://doi.org/10.5281/zenodo.8145320Test; oai:zenodo.org:8145320 |
| DOI: | 10.5281/zenodo.8145320 |
| الإتاحة: | https://doi.org/10.5281/zenodo.8145320Test https://doi.org/10.5281/zenodo.8145319Test https://zenodo.org/record/8145320Test |
| حقوق: | info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0/legalcodeTest |
| رقم الانضمام: | edsbas.7A2917FE |
| قاعدة البيانات: | BASE |
| DOI: | 10.5281/zenodo.8145320 |
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