Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia

Autores
Tomasella, María Eugenia; Falasco, Germán Alfredo; Urrutia, Leandro; Bechelli, Maria Lucila; Padilla Franzotti, Carla Luciana; Gelman, Diego Matias
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Schizophrenia is a disease diagnosed by visible signs and symptoms from late adolescence to early adulthood. The etiology of this disease remains unknown. An objective diagnostic approach is required. Here, we used a mouse model that shows schizophrenia-like phenotypes to study brain glucose metabolism and presynaptic dopaminergic functioning by positron emission tomography (PET) and immunohistochemistry. PET scannings were performed on mice after the administration of [18F]-FDG or [18F]-F-DOPA. Glucose metabolism was evaluated in basal conditions and after the induction of a hyperdopaminergic state.Results: Mutant animals show reduced glucose metabolism in prefrontal cortex, amygdala, and nucleus reuniens under the hyperdopaminergic state. They also show reduced [18F]-F-DOPA uptake in prefrontal cortex, substantia nigra reticulata, raphe nucleus, and ventral striatum but increased [18F]-F-DOPA uptake in dorsal striatum. Mutant animals also show reduced tyrosine hydroxylase expression on midbrain neurons.Conclusions: Dopamine D2 mutant animals show reduced glucose metabolism and impaired presynaptic dopaminergic functioning, in line with reports from human studies. This mouse line may be a valuable model of schizophrenia, useful to test novel tracers for PET scanning diagnostic.
Fil: Tomasella, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Falasco, Germán Alfredo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Urrutia, Leandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Bechelli, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Padilla Franzotti, Carla Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
DOPAMINE
GLUCOSE METABOLISM
MOUSE MODEL
PET
SCHIZOPHRENIA
18F-DOPA
18FDG
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/111480
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/111480
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophreniaTomasella, María EugeniaFalasco, Germán AlfredoUrrutia, LeandroBechelli, Maria LucilaPadilla Franzotti, Carla LucianaGelman, Diego MatiasDOPAMINEGLUCOSE METABOLISMMOUSE MODELPETSCHIZOPHRENIA18F-DOPA18FDGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Schizophrenia is a disease diagnosed by visible signs and symptoms from late adolescence to early adulthood. The etiology of this disease remains unknown. An objective diagnostic approach is required. Here, we used a mouse model that shows schizophrenia-like phenotypes to study brain glucose metabolism and presynaptic dopaminergic functioning by positron emission tomography (PET) and immunohistochemistry. PET scannings were performed on mice after the administration of [18F]-FDG or [18F]-F-DOPA. Glucose metabolism was evaluated in basal conditions and after the induction of a hyperdopaminergic state.Results: Mutant animals show reduced glucose metabolism in prefrontal cortex, amygdala, and nucleus reuniens under the hyperdopaminergic state. They also show reduced [18F]-F-DOPA uptake in prefrontal cortex, substantia nigra reticulata, raphe nucleus, and ventral striatum but increased [18F]-F-DOPA uptake in dorsal striatum. Mutant animals also show reduced tyrosine hydroxylase expression on midbrain neurons.Conclusions: Dopamine D2 mutant animals show reduced glucose metabolism and impaired presynaptic dopaminergic functioning, in line with reports from human studies. This mouse line may be a valuable model of schizophrenia, useful to test novel tracers for PET scanning diagnostic.Fil: Tomasella, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Falasco, Germán Alfredo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Urrutia, Leandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Bechelli, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Padilla Franzotti, Carla Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaSpringer2020-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/111480Tomasella, María Eugenia; Falasco, Germán Alfredo; Urrutia, Leandro; Bechelli, Maria Lucila; Padilla Franzotti, Carla Luciana; et al.; Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia; Springer; European Journal of Nuclear Medicine and Molecular Imaging Research; 10; 39; 4-2020; 1-92191-219XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://ejnmmires.springeropen.com/articles/10.1186/s13550-020-00629-xinfo:eu-repo/semantics/altIdentifier/doi/10.1186/s13550-020-00629-xinfo:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165233/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:35:10Zoai:ri.conicet.gov.ar:11336/111480instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:35:10.964CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
title Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
spellingShingle Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
Tomasella, María Eugenia
DOPAMINE
GLUCOSE METABOLISM
MOUSE MODEL
PET
SCHIZOPHRENIA
18F-DOPA
18FDG
title_short Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
title_full Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
title_fullStr Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
title_full_unstemmed Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
title_sort Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia
dc.creator.none.fl_str_mv Tomasella, María Eugenia
Falasco, Germán Alfredo
Urrutia, Leandro
Bechelli, Maria Lucila
Padilla Franzotti, Carla Luciana
Gelman, Diego Matias
author Tomasella, María Eugenia
author_facet Tomasella, María Eugenia
Falasco, Germán Alfredo
Urrutia, Leandro
Bechelli, Maria Lucila
Padilla Franzotti, Carla Luciana
Gelman, Diego Matias
author_role author
author2 Falasco, Germán Alfredo
Urrutia, Leandro
Bechelli, Maria Lucila
Padilla Franzotti, Carla Luciana
Gelman, Diego Matias
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv DOPAMINE
GLUCOSE METABOLISM
MOUSE MODEL
PET
SCHIZOPHRENIA
18F-DOPA
18FDG
topic DOPAMINE
GLUCOSE METABOLISM
MOUSE MODEL
PET
SCHIZOPHRENIA
18F-DOPA
18FDG
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Schizophrenia is a disease diagnosed by visible signs and symptoms from late adolescence to early adulthood. The etiology of this disease remains unknown. An objective diagnostic approach is required. Here, we used a mouse model that shows schizophrenia-like phenotypes to study brain glucose metabolism and presynaptic dopaminergic functioning by positron emission tomography (PET) and immunohistochemistry. PET scannings were performed on mice after the administration of [18F]-FDG or [18F]-F-DOPA. Glucose metabolism was evaluated in basal conditions and after the induction of a hyperdopaminergic state.Results: Mutant animals show reduced glucose metabolism in prefrontal cortex, amygdala, and nucleus reuniens under the hyperdopaminergic state. They also show reduced [18F]-F-DOPA uptake in prefrontal cortex, substantia nigra reticulata, raphe nucleus, and ventral striatum but increased [18F]-F-DOPA uptake in dorsal striatum. Mutant animals also show reduced tyrosine hydroxylase expression on midbrain neurons.Conclusions: Dopamine D2 mutant animals show reduced glucose metabolism and impaired presynaptic dopaminergic functioning, in line with reports from human studies. This mouse line may be a valuable model of schizophrenia, useful to test novel tracers for PET scanning diagnostic.
Fil: Tomasella, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Falasco, Germán Alfredo. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Urrutia, Leandro. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Bechelli, Maria Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Padilla Franzotti, Carla Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Gelman, Diego Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Background: Schizophrenia is a disease diagnosed by visible signs and symptoms from late adolescence to early adulthood. The etiology of this disease remains unknown. An objective diagnostic approach is required. Here, we used a mouse model that shows schizophrenia-like phenotypes to study brain glucose metabolism and presynaptic dopaminergic functioning by positron emission tomography (PET) and immunohistochemistry. PET scannings were performed on mice after the administration of [18F]-FDG or [18F]-F-DOPA. Glucose metabolism was evaluated in basal conditions and after the induction of a hyperdopaminergic state.Results: Mutant animals show reduced glucose metabolism in prefrontal cortex, amygdala, and nucleus reuniens under the hyperdopaminergic state. They also show reduced [18F]-F-DOPA uptake in prefrontal cortex, substantia nigra reticulata, raphe nucleus, and ventral striatum but increased [18F]-F-DOPA uptake in dorsal striatum. Mutant animals also show reduced tyrosine hydroxylase expression on midbrain neurons.Conclusions: Dopamine D2 mutant animals show reduced glucose metabolism and impaired presynaptic dopaminergic functioning, in line with reports from human studies. This mouse line may be a valuable model of schizophrenia, useful to test novel tracers for PET scanning diagnostic.
publishDate 2020
dc.date.none.fl_str_mv 2020-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/111480
Tomasella, María Eugenia; Falasco, Germán Alfredo; Urrutia, Leandro; Bechelli, Maria Lucila; Padilla Franzotti, Carla Luciana; et al.; Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia; Springer; European Journal of Nuclear Medicine and Molecular Imaging Research; 10; 39; 4-2020; 1-9
2191-219X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/111480
identifier_str_mv Tomasella, María Eugenia; Falasco, Germán Alfredo; Urrutia, Leandro; Bechelli, Maria Lucila; Padilla Franzotti, Carla Luciana; et al.; Impaired brain glucose metabolism and presynaptic dopaminergic functioning in a mouse model of schizophrenia; Springer; European Journal of Nuclear Medicine and Molecular Imaging Research; 10; 39; 4-2020; 1-9
2191-219X
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://ejnmmires.springeropen.com/articles/10.1186/s13550-020-00629-x
info:eu-repo/semantics/altIdentifier/doi/10.1186/s13550-020-00629-x
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165233/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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