NMDARs Mediate the Role of Monoamine Oxidase A in Pathological Aggression
| العنوان: | NMDARs Mediate the Role of Monoamine Oxidase A in Pathological Aggression |
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| المؤلفون: | Giovanna Flore, Maria Paola Castelli, Alessio Soggiu, Miriam Melis, Marco Bortolato, Paola Roncada, Andrea Urbani, Paola Devoto, Angelo Casu, Jc Shih, Sc Godar, Kevin Chen, Roberto Frau |
| المصدر: | Journal of Neuroscience. 32:8574-8582 |
| بيانات النشر: | Society for Neuroscience, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Male, Patch-Clamp Techniques, Hippocampus, Mice, Norepinephrine, chemistry.chemical_compound, Piperidines, Receptors, Prefrontal cortex, PEAQX, Mice, Knockout, biology, Blotting, Settore BIO/12, General Neuroscience, Glutamate receptor, Antisocial Personality Disorder, Aggression, NMDA receptor, Monoamine oxidase A, Psychology, Western, N-Methyl-D-Aspartate, medicine.drug, Serotonin, medicine.medical_specialty, Monoamine oxidase, Knockout, Blotting, Western, Glutamic Acid, Animals, Autoradiography, Dizocilpine Maleate, Receptors, N-Methyl-D-Aspartate, Prosencephalon, Excitatory Amino Acid Antagonists, Corpus Striatum, Monoamine Oxidase, Phenols, Binding Sites, Motor Activity, Quinoxalines, Electrophysiological Phenomena, Article, Internal medicine, medicine, Dizocilpine, Endocrinology, nervous system, chemistry, biology.protein, Neuroscience |
| الوصف: | Converging evidence shows that monoamine oxidase A (MAO A), the key enzyme catalyzing serotonin (5-hydroxytryptamine; 5-HT) and norepinephrine (NE) degradation, is a primary factor in the pathophysiology of antisocial and aggressive behavior. Accordingly, male MAO A-deficient humans and mice exhibit an extreme predisposition to aggressive outbursts in response to stress. As NMDARs regulate the emotional reactivity to social and environmental stimuli, we hypothesized their involvement in the modulation of aggression mediated by MAO A. In comparison with WT male mice, MAO A KO counterparts exhibited increases in 5-HT and NE levels across all brain regions, but no difference in glutamate concentrations and NMDAR binding. Notably, the prefrontal cortex (PFC) of MAO A KO mice exhibited higher expression of NR2A and NR2B, as well as lower levels of glycosylated NR1 subunits. In line with these changes, the current amplitude and decay time of NMDARs in PFC was significantly reduced. Furthermore, the currents of these receptors were hypersensitive to the action of the antagonists of the NMDAR complex (dizocilpine), as well as NR2A (PEAQX) and NR2B (Ro 25–6981) subunits. Notably, systemic administration of these agents selectively countered the enhanced aggression in MAO A KO mice, at doses that did not inherently affect motor activity. Our findings suggest that the role of MAO A in pathological aggression may be mediated by changes in NMDAR subunit composition in the PFC, and point to a critical function of this receptor in the molecular bases of antisocial personality. |
| تدمد: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0225-12.2012 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c3dd0ccca139853474096a4552a3c74f https://doi.org/10.1523/jneurosci.0225-12.2012 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c3dd0ccca139853474096a4552a3c74f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15292401 02706474 |
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| DOI: | 10.1523/jneurosci.0225-12.2012 |