Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?

Autores
Maniscalchi Velásquez, Athina del Valle; Benzi Juncos, Oriana Nicole; Funk, Melania Iara; Conde, Melisa Ailén; Bonjour, Mariel; Alza, Natalia Paola; Salvador, Gabriela Alejandra
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
We have previously established an in vivo iron overload model using C57BL/6 mice characterized by movement disorders similar to Parkinson’s disease phenotype. Midbrain analysis of iron-treated mice showed increased gliosis along with the loss of tyrosine hydroxylase labeling and the presence of ferroptosis markers. Associated with dopaminergic neuronal loss, we found cholesterol (Chol) accumulation in the midbrain (p<0.05). Free Chol increase was accompanied by the upregulation of SREBP1 and SREBP2 (p<0.001) transcription factors. To further investigate the link between Chol and ferroptosis, we used single-cell cultures of neurons, astrocytes, microglia, and primary glial cultures exposed to iron overload. Dopaminergic neurons (N27), astrocytes (C6), and mouse primary glial cultures showed increased Chol levels in intracellular compartments as well as in their secretomes after iron treatment (p<0.001). This rise coincided with the upregulation of genes associated with Chol de novo synthesis and transport, HMGCR and ABCA1 (p<0.001). In addition, neurons incubated with astrocytes’ secretome enhanced even more their Chol content, probably due to the upregulation of the ABCA1 transporter. To study the link between Chol accumulation and ferroptosis, cells were exposed to the inhibitor ferrostatin-1. We found that ferrostatin-1 reduced Chol levels when cells were exposed to iron overload (p<0.001). Our findings indicate that altered Chol metabolism could be a biomarker of midbrain neurodegeneration triggered by ferroptosis, with motor impairment as an outcome
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
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: 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: Bonjour, Mariel. 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
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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
LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental
Materia
CHOLESTEROL
FERROPTOSIS
MOVEMENT DISORDERS
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:11336/278515
Acceder
id CONICETDig_e90b34150b248cbca337cc92d97d7722
oai_identifier_str oai:ri.conicet.gov.ar:11336/278515
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?Maniscalchi Velásquez, Athina del ValleBenzi Juncos, Oriana NicoleFunk, Melania IaraConde, Melisa AilénBonjour, MarielAlza, Natalia PaolaSalvador, Gabriela AlejandraCHOLESTEROLFERROPTOSISMOVEMENT DISORDERSMIDBRAINhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1We have previously established an in vivo iron overload model using C57BL/6 mice characterized by movement disorders similar to Parkinson’s disease phenotype. Midbrain analysis of iron-treated mice showed increased gliosis along with the loss of tyrosine hydroxylase labeling and the presence of ferroptosis markers. Associated with dopaminergic neuronal loss, we found cholesterol (Chol) accumulation in the midbrain (p<0.05). Free Chol increase was accompanied by the upregulation of SREBP1 and SREBP2 (p<0.001) transcription factors. To further investigate the link between Chol and ferroptosis, we used single-cell cultures of neurons, astrocytes, microglia, and primary glial cultures exposed to iron overload. Dopaminergic neurons (N27), astrocytes (C6), and mouse primary glial cultures showed increased Chol levels in intracellular compartments as well as in their secretomes after iron treatment (p<0.001). This rise coincided with the upregulation of genes associated with Chol de novo synthesis and transport, HMGCR and ABCA1 (p<0.001). In addition, neurons incubated with astrocytes’ secretome enhanced even more their Chol content, probably due to the upregulation of the ABCA1 transporter. To study the link between Chol accumulation and ferroptosis, cells were exposed to the inhibitor ferrostatin-1. We found that ferrostatin-1 reduced Chol levels when cells were exposed to iron overload (p<0.001). Our findings indicate that altered Chol metabolism could be a biomarker of midbrain neurodegeneration triggered by ferroptosis, with motor impairment as an outcomeFil: 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; 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: 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: Bonjour, Mariel. 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; 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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; ArgentinaLVI Reunión Anual De La Asociación Argentina De Farmacología ExperimentalBahía BlancaArgentinaAsociación Argentina De Farmacología ExperimentalAsociación Argentina De Farmacología Experimental2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/278515Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration? ; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental ; Bahía Blanca; Argentina; 2024; 111-111CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://aafeargentina.org/congresos-aafe/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-02-26T10:10:42Zoai:ri.conicet.gov.ar:11336/278515instacron: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:34982026-02-26 10:10:42.397CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
title Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
spellingShingle Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
Maniscalchi Velásquez, Athina del Valle
CHOLESTEROL
FERROPTOSIS
MOVEMENT DISORDERS
MIDBRAIN
title_short Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
title_full Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
title_fullStr Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
title_full_unstemmed Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
title_sort Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration?
dc.creator.none.fl_str_mv Maniscalchi Velásquez, Athina del Valle
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Conde, Melisa Ailén
Bonjour, Mariel
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author Maniscalchi Velásquez, Athina del Valle
author_facet Maniscalchi Velásquez, Athina del Valle
Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Conde, Melisa Ailén
Bonjour, Mariel
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author_role author
author2 Benzi Juncos, Oriana Nicole
Funk, Melania Iara
Conde, Melisa Ailén
Bonjour, Mariel
Alza, Natalia Paola
Salvador, Gabriela Alejandra
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHOLESTEROL
FERROPTOSIS
MOVEMENT DISORDERS
MIDBRAIN
topic CHOLESTEROL
FERROPTOSIS
MOVEMENT DISORDERS
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 We have previously established an in vivo iron overload model using C57BL/6 mice characterized by movement disorders similar to Parkinson’s disease phenotype. Midbrain analysis of iron-treated mice showed increased gliosis along with the loss of tyrosine hydroxylase labeling and the presence of ferroptosis markers. Associated with dopaminergic neuronal loss, we found cholesterol (Chol) accumulation in the midbrain (p<0.05). Free Chol increase was accompanied by the upregulation of SREBP1 and SREBP2 (p<0.001) transcription factors. To further investigate the link between Chol and ferroptosis, we used single-cell cultures of neurons, astrocytes, microglia, and primary glial cultures exposed to iron overload. Dopaminergic neurons (N27), astrocytes (C6), and mouse primary glial cultures showed increased Chol levels in intracellular compartments as well as in their secretomes after iron treatment (p<0.001). This rise coincided with the upregulation of genes associated with Chol de novo synthesis and transport, HMGCR and ABCA1 (p<0.001). In addition, neurons incubated with astrocytes’ secretome enhanced even more their Chol content, probably due to the upregulation of the ABCA1 transporter. To study the link between Chol accumulation and ferroptosis, cells were exposed to the inhibitor ferrostatin-1. We found that ferrostatin-1 reduced Chol levels when cells were exposed to iron overload (p<0.001). Our findings indicate that altered Chol metabolism could be a biomarker of midbrain neurodegeneration triggered by ferroptosis, with motor impairment as an outcome
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
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: 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: Bonjour, Mariel. 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
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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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
LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental
Bahía Blanca
Argentina
Asociación Argentina De Farmacología Experimental
description We have previously established an in vivo iron overload model using C57BL/6 mice characterized by movement disorders similar to Parkinson’s disease phenotype. Midbrain analysis of iron-treated mice showed increased gliosis along with the loss of tyrosine hydroxylase labeling and the presence of ferroptosis markers. Associated with dopaminergic neuronal loss, we found cholesterol (Chol) accumulation in the midbrain (p<0.05). Free Chol increase was accompanied by the upregulation of SREBP1 and SREBP2 (p<0.001) transcription factors. To further investigate the link between Chol and ferroptosis, we used single-cell cultures of neurons, astrocytes, microglia, and primary glial cultures exposed to iron overload. Dopaminergic neurons (N27), astrocytes (C6), and mouse primary glial cultures showed increased Chol levels in intracellular compartments as well as in their secretomes after iron treatment (p<0.001). This rise coincided with the upregulation of genes associated with Chol de novo synthesis and transport, HMGCR and ABCA1 (p<0.001). In addition, neurons incubated with astrocytes’ secretome enhanced even more their Chol content, probably due to the upregulation of the ABCA1 transporter. To study the link between Chol accumulation and ferroptosis, cells were exposed to the inhibitor ferrostatin-1. We found that ferrostatin-1 reduced Chol levels when cells were exposed to iron overload (p<0.001). Our findings indicate that altered Chol metabolism could be a biomarker of midbrain neurodegeneration triggered by ferroptosis, with motor impairment as an outcome
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
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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/11336/278515
Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration? ; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental ; Bahía Blanca; Argentina; 2024; 111-111
CONICET Digital
CONICET
url http://hdl.handle.net/11336/278515
identifier_str_mv Cholesterol Metabolism Impairment: A Biomarker Of Neurodegeneration? ; LVI Reunión Anual De La Asociación Argentina De Farmacología Experimental ; Bahía Blanca; Argentina; 2024; 111-111
CONICET Digital
CONICET
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language eng
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dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Asociación Argentina De Farmacología Experimental
publisher.none.fl_str_mv Asociación Argentina De Farmacología Experimental
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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