Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice relevance to schizophrenia
| Autor: | José L. M. Madrigal, Manuel Desco, Angel Pazos, M J Guerrero, Alfonso Gutiérrez-Adán, Elena Castro, Javier Pascau, J. Javier Meana, Juan C. Leza, Javier Garzón, Juan Antonio Mico, Eva Munarriz-Cuezva, Leyre Urigüen, María Luisa Soto-Montenegro, Pilar Sánchez-Blázquez, Jesús A. García-Sevilla, Jorge E. Ortega, Itziar Gil-Pisa, Esther Berrocoso, Belén Pintado, Marcel Ferrer-Alcón |
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| Přispěvatelé: | Centro de Investigación Biomédica en Red Salud Mental (España), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Eusko Jaurlaritza, Universidad del País Vasco, Federación Española de Enfermedades Raras, Universidad Complutense de Madrid |
| Rok vydání: | 2013 |
| Předmět: |
Genetically modified mouse
Reflex Startle PPI Dopamine Microdialysis Mice Transgenic Striatum Motor Activity Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Munc18 Proteins Neurochemical medicine PPI schizophrenia Animals Humans Social Behavior Neurotransmitter Biological Psychiatry Prepulse inhibition Nerve Fibers Unmyelinated Behavior Animal Caspase 3 CELLULAR AND MOLECULAR NEUROSCIENCE PSYCHIATRY AND MENTAL HEALTH Brain Recognition Psychology Organ Size Munc18-1a Startle reaction Mice Inbred C57BL schizophrenia Disease Models Animal Psychiatry and Mental health Phenotype chemistry SNARE Original Article munc18-1a Lipid Peroxidation Psychopharmacology SNARE Proteins Psychology Neuroscience BIOLOGICAL PSYCHIATRY medicine.drug |
| Zdroj: | Repositorio de Resultados de Investigación del INIA INIA: Repositorio de Resultados de Investigación del INIA Digital.CSIC. Repositorio Institucional del CSIC instname Translational Psychiatry Addi. Archivo Digital para la Docencia y la Investigación Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria INIA |
| ISSN: | 2009-0846 |
| Popis: | This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License.-- et al. Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D(1) receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia. The animal could provide valuable insights into phenotypic aspects of this psychiatric disorder. The study was supported by an intramural Grant from Centro de Investigación Biomédica en Red de Salud Mental, Instituto de Salud Carlos III (CIBERSAM), Spanish MICINN and FEDER (SAF2009-08460 to JJM; SAF2010-21948 to JLMMM; AGL2009-11358 to AG-A, SAF2011-29918 to JAGS; PI10/02986, CP08/00017 and CEN-20101014 to MD), Basque Government (S-PR10UN01 to JEO and IT-199/07 to JJM), University of the Basque Country (UPV/EHU) and Complutense University of Madrid (UCM GR42/10-962075 to JLMM). |
| Databáze: | OpenAIRE |
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