Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

• Published in: Translational psychiatry Vol. 3; no. 1; p. e221
• Main Authors: Urigüen, L, Gil-Pisa, I, Munarriz-Cuezva, E, Berrocoso, E, Pascau, J, Soto-Montenegro, M L, Gutiérrez-Adán, A, Pintado, B, Madrigal, J L M, Castro, E, Sánchez-Blázquez, P, Ortega, J E, Guerrero, M J, Ferrer-Alcon, M, García-Sevilla, J A, Micó, J A, Desco, M, Leza, J C, Pazos, Á, Garzón, J, Meana, J J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2013; Nature Publishing Group
• Subjects: 631/1647/767/1424; 692/420; 692/699/476/1799; Animals; Behavior, Animal - physiology; Behavioral Sciences; Biological Psychology; Brain - metabolism; Caspase 3 - metabolism; Disease Models, Animal; Dopamine - metabolism; Humans; Lipid Peroxidation - genetics; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microdialysis; Motor Activity - genetics; Munc18 Proteins - genetics; Munc18 Proteins - metabolism; Nerve Fibers, Unmyelinated - pathology; Neurosciences; Organ Size - genetics; Original; original-article; Pharmacotherapy; Phenotype; Psychiatry; Recognition (Psychology) - physiology; Reflex, Startle - genetics; Schizophrenia - metabolism; SNARE Proteins - metabolism; Social Behavior; PPI; Munc18-1a; schizophrenia; SNARE
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2012.149

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.