Subcortical dopaminergic deficits in a DISC1 mutant model: a study in direct reference to human molecular brain imaging
Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systemati...
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| Veröffentlicht in: | Human molecular genetics 2013-04, Vol.22 (8), p.1574-1580 |
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| creator | Jaaro-Peled, Hanna Niwa, Minae Foss, Catherine A Murai, Rina de Los Reyes, Samantha Kamiya, Atsushi Mateo, Yolanda O'Donnell, Patricio Cascella, Nicola G Nabeshima, Toshitaka Guilarte, Tomás R Pomper, Martin G Sawa, Akira |
| description | Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging. |
| doi_str_mv | 10.1093/hmg/ddt007 |
| format | Article |
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Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddt007</identifier><identifier>PMID: 23314019</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Brain - diagnostic imaging ; Brain - metabolism ; Brain Mapping ; Corpus Striatum - metabolism ; Corpus Striatum - ultrastructure ; Dopamine - genetics ; Dopamine - metabolism ; Humans ; Methamphetamine - administration & dosage ; Mice ; Mice, Transgenic ; Molecular Imaging ; Mutation ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Positron-Emission Tomography - methods ; Protein Binding ; Radiography ; Receptors, Dopamine D2 - genetics ; Receptors, Dopamine D2 - isolation & purification ; Receptors, Dopamine D2 - metabolism</subject><ispartof>Human molecular genetics, 2013-04, Vol.22 (8), p.1574-1580</ispartof><rights>The Author 2013. 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Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration. Previously we reported that this model displayed deficits in the forced swim test, a representative indicator of antidepressant efficacy. By combining the results of our two studies, we propose a working hypothesis for future studies that this model might represent a mixed condition of depression and psychosis. We hope that this study will also help bridge a major gap in translational psychiatry between basic characterization of animal models and clinico-pharmacological assessment of patients mainly through PET imaging.</description><subject>Animals</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - metabolism</subject><subject>Brain Mapping</subject><subject>Corpus Striatum - metabolism</subject><subject>Corpus Striatum - ultrastructure</subject><subject>Dopamine - genetics</subject><subject>Dopamine - metabolism</subject><subject>Humans</subject><subject>Methamphetamine - administration & dosage</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Molecular Imaging</subject><subject>Mutation</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Positron-Emission Tomography - methods</subject><subject>Protein Binding</subject><subject>Radiography</subject><subject>Receptors, Dopamine D2 - genetics</subject><subject>Receptors, Dopamine D2 - isolation & purification</subject><subject>Receptors, Dopamine D2 - metabolism</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS0EokvhwgdAPiKk0Jk4cWIOSGj5V6kSh8LZcuxJ1ihxFtsB9dvjaksFN06jmfnpaeY9xp4jvEZQ4uKwTBfOZYDuAdthI6GqoRcP2Q6UbCqpQJ6xJyl9B0DZiO4xO6uFwAZQ7div622wa8zempm79WgWHyhO3nJHo7c-J-4DN_z95fUe-bJlEzJfVkfzmzJNeXM3t4DzkWzmkUaKFCzxvPLDtphQ2JnsNpvIh2gK6Rcz-TA9ZY9GMyd6dlfP2bePH77uP1dXXz5d7t9dVbbpulyZplZDbxFHbGWDaOzQIoyuFqUH1zkaXAudUagUCGdIyaF40gC1tVJSinP29qR73IaFnKWQo5n1MZY74o1ejdf_boI_6Gn9qYWEthd1EXh5JxDXHxulrBefLM2zCbRuSaOo-xZ70XX_gaKS2MseC_rqhNq4plRsu78IQd-Gqkuo-hRqgV_8_cM9-idF8Rv64Z8C</recordid><startdate>20130415</startdate><enddate>20130415</enddate><creator>Jaaro-Peled, Hanna</creator><creator>Niwa, Minae</creator><creator>Foss, Catherine A</creator><creator>Murai, Rina</creator><creator>de Los Reyes, Samantha</creator><creator>Kamiya, Atsushi</creator><creator>Mateo, Yolanda</creator><creator>O'Donnell, Patricio</creator><creator>Cascella, Nicola G</creator><creator>Nabeshima, Toshitaka</creator><creator>Guilarte, Tomás R</creator><creator>Pomper, Martin G</creator><creator>Sawa, Akira</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20130415</creationdate><title>Subcortical dopaminergic deficits in a DISC1 mutant model: a study in direct reference to human molecular brain imaging</title><author>Jaaro-Peled, Hanna ; Niwa, Minae ; Foss, Catherine A ; Murai, Rina ; de Los Reyes, Samantha ; Kamiya, Atsushi ; Mateo, Yolanda ; O'Donnell, Patricio ; Cascella, Nicola G ; Nabeshima, Toshitaka ; Guilarte, Tomás R ; Pomper, Martin G ; Sawa, Akira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c477t-a429b8c11f156411acb510fd231560d7debd507a919903dae96b10940e5299663</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - metabolism</topic><topic>Brain Mapping</topic><topic>Corpus Striatum - metabolism</topic><topic>Corpus Striatum - ultrastructure</topic><topic>Dopamine - genetics</topic><topic>Dopamine - metabolism</topic><topic>Humans</topic><topic>Methamphetamine - administration & dosage</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>Molecular Imaging</topic><topic>Mutation</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Positron-Emission Tomography - methods</topic><topic>Protein Binding</topic><topic>Radiography</topic><topic>Receptors, Dopamine D2 - genetics</topic><topic>Receptors, Dopamine D2 - isolation & purification</topic><topic>Receptors, Dopamine D2 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jaaro-Peled, Hanna</creatorcontrib><creatorcontrib>Niwa, Minae</creatorcontrib><creatorcontrib>Foss, Catherine A</creatorcontrib><creatorcontrib>Murai, Rina</creatorcontrib><creatorcontrib>de Los Reyes, Samantha</creatorcontrib><creatorcontrib>Kamiya, Atsushi</creatorcontrib><creatorcontrib>Mateo, Yolanda</creatorcontrib><creatorcontrib>O'Donnell, Patricio</creatorcontrib><creatorcontrib>Cascella, Nicola G</creatorcontrib><creatorcontrib>Nabeshima, Toshitaka</creatorcontrib><creatorcontrib>Guilarte, Tomás R</creatorcontrib><creatorcontrib>Pomper, Martin G</creatorcontrib><creatorcontrib>Sawa, Akira</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jaaro-Peled, Hanna</au><au>Niwa, Minae</au><au>Foss, Catherine A</au><au>Murai, Rina</au><au>de Los Reyes, Samantha</au><au>Kamiya, Atsushi</au><au>Mateo, Yolanda</au><au>O'Donnell, Patricio</au><au>Cascella, Nicola G</au><au>Nabeshima, Toshitaka</au><au>Guilarte, Tomás R</au><au>Pomper, Martin G</au><au>Sawa, Akira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Subcortical dopaminergic deficits in a DISC1 mutant model: a study in direct reference to human molecular brain imaging</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2013-04-15</date><risdate>2013</risdate><volume>22</volume><issue>8</issue><spage>1574</spage><epage>1580</epage><pages>1574-1580</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. 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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Brain - diagnostic imaging Brain - metabolism Brain Mapping Corpus Striatum - metabolism Corpus Striatum - ultrastructure Dopamine - genetics Dopamine - metabolism Humans Methamphetamine - administration & dosage Mice Mice, Transgenic Molecular Imaging Mutation Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Positron-Emission Tomography - methods Protein Binding Radiography Receptors, Dopamine D2 - genetics Receptors, Dopamine D2 - isolation & purification Receptors, Dopamine D2 - metabolism |
| title | Subcortical dopaminergic deficits in a DISC1 mutant model: a study in direct reference to human molecular brain imaging |
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