Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain

Autores
Maniscalchi Velásquez, Athina del Valle; Conde, Melisa Ailén; Benzi Juncos, Oriana Nicole; Funk, Melania Iara; Alza, Natalia Paola; Salvador, Gabriela Alejandra
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Maneb (MB) is a widely used dithiocarbamate fungicide that can cross the blood-brain barrier and has been reported as an environmental triggering factor of Parkinson’s disease. In a previous work, we demonstrated that MB exposure induced lipid peroxidation in neuronal cultures along with downregulation of glutathione peroxidase 4 (GPX4), and mitochondrial alterations. These previous findings were indicative markers of a specific regulated cell death mechanism named ferroptosis. In the present work, we aimed to characterize MB-induced neurotoxicity in midbrain using C57BL/6 mice exposed to the pesticide. In this in vivo model we studied biochemical changes associated with lipid metabolism. In the midbrain of MB-treated animals, oxidative stress and astrogliosis were accompanied by the loss of tyrosine hydroxylase-positive neurons, and an enhanced expression of α-synuclein. Regarding markers of ferroptosis, MB promoted lipid peroxidation with reduced glutathione content and decreased mRNA expression of GPX4 and the cystine/glutamate transporter SLC7A11. In addition, cholesterol accumulation was accompanied by the upregulation of genes associated with its metabolism, such as Srebp-2 and Hmgcr. Behavioral tests showed that MB treatment impaired mice's locomotor activity. The total distance traveled, supported and unsupported rears were lessened during the open field test in MB-treated mice, and they additionally displayed a diminished rotarod performance. Overall, we established a mouse model of pesticide exposure with a neurodegenerative phenotype that points towards a link between midbrain ferroptosis and colesterol metabolism disturbances.
Fil: Maniscalchi Velásquez, Athina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Funk, Melania Iara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research
Córdoba
Argentina
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
Materia
PESTICIDE
NEUROTOXICITY
CHOLESTEROL
MIDBRAIN
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:11336/278767
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/278767
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse MidbrainManiscalchi Velásquez, Athina del ValleConde, Melisa AilénBenzi Juncos, Oriana NicoleFunk, Melania IaraAlza, Natalia PaolaSalvador, Gabriela AlejandraPESTICIDENEUROTOXICITYCHOLESTEROLMIDBRAINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Maneb (MB) is a widely used dithiocarbamate fungicide that can cross the blood-brain barrier and has been reported as an environmental triggering factor of Parkinson’s disease. In a previous work, we demonstrated that MB exposure induced lipid peroxidation in neuronal cultures along with downregulation of glutathione peroxidase 4 (GPX4), and mitochondrial alterations. These previous findings were indicative markers of a specific regulated cell death mechanism named ferroptosis. In the present work, we aimed to characterize MB-induced neurotoxicity in midbrain using C57BL/6 mice exposed to the pesticide. In this in vivo model we studied biochemical changes associated with lipid metabolism. In the midbrain of MB-treated animals, oxidative stress and astrogliosis were accompanied by the loss of tyrosine hydroxylase-positive neurons, and an enhanced expression of α-synuclein. Regarding markers of ferroptosis, MB promoted lipid peroxidation with reduced glutathione content and decreased mRNA expression of GPX4 and the cystine/glutamate transporter SLC7A11. In addition, cholesterol accumulation was accompanied by the upregulation of genes associated with its metabolism, such as Srebp-2 and Hmgcr. Behavioral tests showed that MB treatment impaired mice's locomotor activity. The total distance traveled, supported and unsupported rears were lessened during the open field test in MB-treated mice, and they additionally displayed a diminished rotarod performance. Overall, we established a mouse model of pesticide exposure with a neurodegenerative phenotype that points towards a link between midbrain ferroptosis and colesterol metabolism disturbances.Fil: Maniscalchi Velásquez, Athina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Funk, Melania Iara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology ResearchCórdobaArgentinaSociedad Argentina de Investigaciones en Bioquímica y Biología MolecularSociedad Argentina de Investigaciones en Bioquímica y Biología Molecular2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278767Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain; LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; Córdoba; Argentina; 2024; 99-99CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saib.org.ar/archivos/2024/abstracts-EN.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-06T12:02:15Zoai:ri.conicet.gov.ar:11336/278767instacron: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:34982026-02-06 12:02:15.917CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
title Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
spellingShingle Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
Maniscalchi Velásquez, Athina del Valle
PESTICIDE
NEUROTOXICITY
CHOLESTEROL
MIDBRAIN
title_short Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
title_full Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
title_fullStr Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
title_full_unstemmed Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
title_sort Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain
dc.creator.none.fl_str_mv Maniscalchi Velásquez, Athina del Valle
Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author Maniscalchi Velásquez, Athina del Valle
author_facet Maniscalchi Velásquez, Athina del Valle
Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author_role author
author2 Conde, Melisa Ailén
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv PESTICIDE
NEUROTOXICITY
CHOLESTEROL
MIDBRAIN
topic PESTICIDE
NEUROTOXICITY
CHOLESTEROL
MIDBRAIN
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Maneb (MB) is a widely used dithiocarbamate fungicide that can cross the blood-brain barrier and has been reported as an environmental triggering factor of Parkinson’s disease. In a previous work, we demonstrated that MB exposure induced lipid peroxidation in neuronal cultures along with downregulation of glutathione peroxidase 4 (GPX4), and mitochondrial alterations. These previous findings were indicative markers of a specific regulated cell death mechanism named ferroptosis. In the present work, we aimed to characterize MB-induced neurotoxicity in midbrain using C57BL/6 mice exposed to the pesticide. In this in vivo model we studied biochemical changes associated with lipid metabolism. In the midbrain of MB-treated animals, oxidative stress and astrogliosis were accompanied by the loss of tyrosine hydroxylase-positive neurons, and an enhanced expression of α-synuclein. Regarding markers of ferroptosis, MB promoted lipid peroxidation with reduced glutathione content and decreased mRNA expression of GPX4 and the cystine/glutamate transporter SLC7A11. In addition, cholesterol accumulation was accompanied by the upregulation of genes associated with its metabolism, such as Srebp-2 and Hmgcr. Behavioral tests showed that MB treatment impaired mice's locomotor activity. The total distance traveled, supported and unsupported rears were lessened during the open field test in MB-treated mice, and they additionally displayed a diminished rotarod performance. Overall, we established a mouse model of pesticide exposure with a neurodegenerative phenotype that points towards a link between midbrain ferroptosis and colesterol metabolism disturbances.
Fil: Maniscalchi Velásquez, Athina del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Conde, Melisa Ailén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Benzi Juncos, Oriana Nicole. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Funk, Melania Iara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Alza, Natalia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Química; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research
Córdoba
Argentina
Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
description Maneb (MB) is a widely used dithiocarbamate fungicide that can cross the blood-brain barrier and has been reported as an environmental triggering factor of Parkinson’s disease. In a previous work, we demonstrated that MB exposure induced lipid peroxidation in neuronal cultures along with downregulation of glutathione peroxidase 4 (GPX4), and mitochondrial alterations. These previous findings were indicative markers of a specific regulated cell death mechanism named ferroptosis. In the present work, we aimed to characterize MB-induced neurotoxicity in midbrain using C57BL/6 mice exposed to the pesticide. In this in vivo model we studied biochemical changes associated with lipid metabolism. In the midbrain of MB-treated animals, oxidative stress and astrogliosis were accompanied by the loss of tyrosine hydroxylase-positive neurons, and an enhanced expression of α-synuclein. Regarding markers of ferroptosis, MB promoted lipid peroxidation with reduced glutathione content and decreased mRNA expression of GPX4 and the cystine/glutamate transporter SLC7A11. In addition, cholesterol accumulation was accompanied by the upregulation of genes associated with its metabolism, such as Srebp-2 and Hmgcr. Behavioral tests showed that MB treatment impaired mice's locomotor activity. The total distance traveled, supported and unsupported rears were lessened during the open field test in MB-treated mice, and they additionally displayed a diminished rotarod performance. Overall, we established a mouse model of pesticide exposure with a neurodegenerative phenotype that points towards a link between midbrain ferroptosis and colesterol metabolism disturbances.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/278767
Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain; LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; Córdoba; Argentina; 2024; 99-99
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278767
identifier_str_mv Pesticide-Induced Neurotoxicty Impacts Cholesterol Metabolism In Mouse Midbrain; LX Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; Córdoba; Argentina; 2024; 99-99
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://saib.org.ar/archivos/2024/abstracts-EN.pdf
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/
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application/pdf
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
publisher.none.fl_str_mv Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular
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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