Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes
| العنوان: | Erbb4 Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes |
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| المؤلفون: | Amanda Kiemes, Maria Elisa Serrano Navacerrada, Eugene Kim, Karen Randall, Camilla Simmons, Loreto Rojo Gonzalez, Marija-Magdalena Petrinovic, David J Lythgoe, Diana Rotaru, Davide Di Censo, Lydiane Hirschler, Emmanuel L Barbier, Anthony C Vernon, James M Stone, Cathy Davies, Diana Cash, Gemma Modinos |
| المصدر: | Schizophrenia Bulletin. 49:569-580 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Psychiatry and Mental health |
| الوصف: | Background and Hypothesis Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA α5 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice. Study Design Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F/F, n = 12) and their wild-type littermates (Erbb4F/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography. Results Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified. Conclusions These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species. |
| تدمد: | 1745-1701 0586-7614 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5e1bc4df77b00b9d520b84a4c19e1458 https://doi.org/10.1093/schbul/sbac192 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5e1bc4df77b00b9d520b84a4c19e1458 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17451701 05867614 |
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