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

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 m...

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Published inTranslational 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
LanguageEnglish
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
Online AccessGet full text

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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.
AbstractList 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.
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.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.
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.
Author García-Sevilla, J A
Castro, E
Munarriz-Cuezva, E
Ortega, J E
Gil-Pisa, I
Guerrero, M J
Berrocoso, E
Garzón, J
Madrigal, J L M
Urigüen, L
Gutiérrez-Adán, A
Pintado, B
Sánchez-Blázquez, P
Desco, M
Micó, J A
Ferrer-Alcon, M
Leza, J C
Pazos, Á
Pascau, J
Meana, J J
Soto-Montenegro, M L
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/23340504$$D View this record in MEDLINE/PubMed
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Keywords PPI
Munc18-1a
schizophrenia
SNARE
Language English
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Snippet 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...
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StartPage e221
SubjectTerms 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
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Title Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia
URI https://link.springer.com/article/10.1038/tp.2012.149
https://www.ncbi.nlm.nih.gov/pubmed/23340504
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