BackBehavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia
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Date
2013-01Author
Urigüen Echeverría, Leyre
Gil Pisa, I.
Munarriz Cuezva, Eva
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.
Mico, J. A.
Desco, M.
Leza, Juan Carlos
Pazos, A.
Garzon, J.
Meana Martínez, José Javier 
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Translational Psychiatry 3 : (2013) // e221
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.