title: Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia.
abstract: 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.
authors: Centro de Investigación Biomédica en Red de Salud Mental CIBERSAM, Spain.
authors: L
authors: L
authors: Urigüen
authors: I
authors: I
authors: Gil-Pisa
authors: E
authors: E
authors: Munarriz-Cuezva
authors: E
authors: E
authors: Berrocoso
authors: J
authors: J
authors: Pascau
authors: M L
authors: ML
authors: Soto-Montenegro
authors: A
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authors: Gutiérrez-Adán
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authors: B
authors: Pintado
authors: J L M
authors: JL
authors: Madrigal
authors: E
authors: E
authors: Castro
authors: P
authors: P
authors: Sánchez-Blázquez
authors: J E
authors: JE
authors: Ortega
authors: M J
authors: MJ
authors: Guerrero
authors: M
authors: M
authors: Ferrer-Alcon
authors: J A
authors: JA
authors: García-Sevilla
authors: J A
authors: JA
authors: Micó
authors: M
authors: M
authors: Desco
authors: J C
authors: JC
authors: Leza
authors: A
authors: A
authors: Pazos
authors: J
authors: J
authors: Garzón
authors: J J
authors: JJ
authors: Meana
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017551:Microdialysis; D009043:Motor Activity / Q000235:genetics; D051938:Munc18 Proteins / Q000235:genetics / Q000378:metabolism*; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009929:Organ Size / Q000235:genetics; D010641:Phenotype; D021641:Recognition, Psychology / Q000502:physiology; D013216:Reflex, Startle / Q000235:genetics; D050600:SNARE Proteins / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism*; D012919:Social Behavior
chemical_list: D051938:Munc18 Proteins; D050600:SNARE Proteins; C497938:Stxbp1 protein, mouse; C505409:Casp3 protein, mouse; D053148:Caspase 3; D004298:Dopamine