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	L Urigüen, I Gil-Pisa, E Munarriz-Cuezva, E Berrocoso, J Pascau, M L Soto-Montenegro, A Gutiérrez-Adán, B Pintado, J L M Madrigal, E Castro, P Sánchez-Blázquez, J E Ortega, M J Guerrero, M Ferrer-Alcon, J A García-Sevilla, J A Micó, M Desco, J C Leza, A Pazos, J Garzón, J J Meana
Journal	Translational psychiatry (Transl Psychiatry) Vol. 3 Pg. e221 (Jan 22 2013) ISSN: 2158-3188 [Electronic] United States
PMID	23340504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Munc18 Proteins SNARE Proteins Stxbp1 protein, mouse Casp3 protein, mouse Caspase 3 Dopamine
Topics	Animals Behavior, Animal (physiology) Brain (metabolism) Caspase 3 (metabolism) Disease Models, Animal Dopamine (metabolism) Humans Lipid Peroxidation (genetics) Mice Mice, Inbred C57BL Mice, Transgenic Microdialysis Motor Activity (genetics) Munc18 Proteins (genetics, metabolism) Nerve Fibers, Unmyelinated (pathology) Organ Size (genetics) Phenotype Recognition, Psychology (physiology) Reflex, Startle (genetics) SNARE Proteins (metabolism) Schizophrenia (metabolism) Social Behavior

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