Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice

Autores
Monteleone, Melisa Carolina; Billi, Silvia Cristina; Abarzúa Catalán, Lorena; Henzi, Roberto; Fernandez, Eliana Mailen; Kaehne, Thilo; Wyneken, Ursula; Brocco, Marcela Adriana
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chronic stress can trigger several pathologies including mood disorders for which no clear diagnostic molecular markers have been established yet. Attractive biomarker sources are extracellular vesicles (EVs). Evs are released by cells in health and disease and contain genetic material, proteins and lipids characteristic of the cell state. Here we show that Evs recovered from the blood of animals exposed to a repeated interrupted stress protocol (RIS) have a different protein profile compared to those obtained from control animals. Proteomic analysis indicated that proteins differentially present in bulk serum Evs from stressed animals were implicated in metabolic and inflammatory pathways and several of them were previously related to psychiatric disorders. Interestingly, these serum Evs carry brain-enriched proteins including the stress-responsive neuronal protein M6a. Then, we used an in-utero electroporation strategy to selectively overexpress M6a-GFP in brain neurons and found that M6a-GFP could also be detected in bulk serum Evs suggesting a neuronal origin. Finally, to determine if these Evs could have functional consequences, we administered Evs from control and RIS animals intranasally to naïve mice. Animals receiving stress EVs showed changes in behavior and brain M6a levels similar to those observed in physically stressed animals. Such changes could therefore be attributed, or at least in part, to EV protein transfer. Altogether these findings show that EVs may participate in stress signaling and propose proteins carried by EVs as a valuable source of biomarkers for stress-induced diseases.
Fil: Monteleone, Melisa Carolina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Billi, Silvia Cristina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Abarzúa Catalán, Lorena. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; Chile
Fil: Henzi, Roberto. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; Chile
Fil: Fernandez, Eliana Mailen. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Kaehne, Thilo. Otto-von-Guericke-Universität Magdeburg; Alemania
Fil: Wyneken, Ursula. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; Chile
Fil: Brocco, Marcela Adriana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Materia
EXTRACELLULAR VESICLES
CHRONIC STRESS
GPM6A
PROTEOMICS
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:11336/266524
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive miceMonteleone, Melisa CarolinaBilli, Silvia CristinaAbarzúa Catalán, LorenaHenzi, RobertoFernandez, Eliana MailenKaehne, ThiloWyneken, UrsulaBrocco, Marcela AdrianaEXTRACELLULAR VESICLESCHRONIC STRESSGPM6APROTEOMICShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Chronic stress can trigger several pathologies including mood disorders for which no clear diagnostic molecular markers have been established yet. Attractive biomarker sources are extracellular vesicles (EVs). Evs are released by cells in health and disease and contain genetic material, proteins and lipids characteristic of the cell state. Here we show that Evs recovered from the blood of animals exposed to a repeated interrupted stress protocol (RIS) have a different protein profile compared to those obtained from control animals. Proteomic analysis indicated that proteins differentially present in bulk serum Evs from stressed animals were implicated in metabolic and inflammatory pathways and several of them were previously related to psychiatric disorders. Interestingly, these serum Evs carry brain-enriched proteins including the stress-responsive neuronal protein M6a. Then, we used an in-utero electroporation strategy to selectively overexpress M6a-GFP in brain neurons and found that M6a-GFP could also be detected in bulk serum Evs suggesting a neuronal origin. Finally, to determine if these Evs could have functional consequences, we administered Evs from control and RIS animals intranasally to naïve mice. Animals receiving stress EVs showed changes in behavior and brain M6a levels similar to those observed in physically stressed animals. Such changes could therefore be attributed, or at least in part, to EV protein transfer. Altogether these findings show that EVs may participate in stress signaling and propose proteins carried by EVs as a valuable source of biomarkers for stress-induced diseases.Fil: Monteleone, Melisa Carolina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Billi, Silvia Cristina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Abarzúa Catalán, Lorena. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; ChileFil: Henzi, Roberto. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; ChileFil: Fernandez, Eliana Mailen. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Kaehne, Thilo. Otto-von-Guericke-Universität Magdeburg; AlemaniaFil: Wyneken, Ursula. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; ChileFil: Brocco, Marcela Adriana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; ArgentinaPublic Library of Science2024-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/266524Monteleone, Melisa Carolina; Billi, Silvia Cristina; Abarzúa Catalán, Lorena; Henzi, Roberto; Fernandez, Eliana Mailen; et al.; Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice; Public Library of Science; Plos One; 19; 8; 8-2024; 1-231932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://dx.plos.org/10.1371/journal.pone.0308976info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0308976info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:28:36Zoai:ri.conicet.gov.ar:11336/266524instacron: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 11:28:37.224CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
title Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
spellingShingle Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
Monteleone, Melisa Carolina
EXTRACELLULAR VESICLES
CHRONIC STRESS
GPM6A
PROTEOMICS
title_short Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
title_full Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
title_fullStr Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
title_full_unstemmed Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
title_sort Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice
dc.creator.none.fl_str_mv Monteleone, Melisa Carolina
Billi, Silvia Cristina
Abarzúa Catalán, Lorena
Henzi, Roberto
Fernandez, Eliana Mailen
Kaehne, Thilo
Wyneken, Ursula
Brocco, Marcela Adriana
author Monteleone, Melisa Carolina
author_facet Monteleone, Melisa Carolina
Billi, Silvia Cristina
Abarzúa Catalán, Lorena
Henzi, Roberto
Fernandez, Eliana Mailen
Kaehne, Thilo
Wyneken, Ursula
Brocco, Marcela Adriana
author_role author
author2 Billi, Silvia Cristina
Abarzúa Catalán, Lorena
Henzi, Roberto
Fernandez, Eliana Mailen
Kaehne, Thilo
Wyneken, Ursula
Brocco, Marcela Adriana
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv EXTRACELLULAR VESICLES
CHRONIC STRESS
GPM6A
PROTEOMICS
topic EXTRACELLULAR VESICLES
CHRONIC STRESS
GPM6A
PROTEOMICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Chronic stress can trigger several pathologies including mood disorders for which no clear diagnostic molecular markers have been established yet. Attractive biomarker sources are extracellular vesicles (EVs). Evs are released by cells in health and disease and contain genetic material, proteins and lipids characteristic of the cell state. Here we show that Evs recovered from the blood of animals exposed to a repeated interrupted stress protocol (RIS) have a different protein profile compared to those obtained from control animals. Proteomic analysis indicated that proteins differentially present in bulk serum Evs from stressed animals were implicated in metabolic and inflammatory pathways and several of them were previously related to psychiatric disorders. Interestingly, these serum Evs carry brain-enriched proteins including the stress-responsive neuronal protein M6a. Then, we used an in-utero electroporation strategy to selectively overexpress M6a-GFP in brain neurons and found that M6a-GFP could also be detected in bulk serum Evs suggesting a neuronal origin. Finally, to determine if these Evs could have functional consequences, we administered Evs from control and RIS animals intranasally to naïve mice. Animals receiving stress EVs showed changes in behavior and brain M6a levels similar to those observed in physically stressed animals. Such changes could therefore be attributed, or at least in part, to EV protein transfer. Altogether these findings show that EVs may participate in stress signaling and propose proteins carried by EVs as a valuable source of biomarkers for stress-induced diseases.
Fil: Monteleone, Melisa Carolina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Billi, Silvia Cristina. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Abarzúa Catalán, Lorena. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; Chile
Fil: Henzi, Roberto. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; Chile
Fil: Fernandez, Eliana Mailen. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Kaehne, Thilo. Otto-von-Guericke-Universität Magdeburg; Alemania
Fil: Wyneken, Ursula. Universidad de Los Andes. Facultad de Medicina. Centro de Investigacion E Innovacion Biomedica.; Chile
Fil: Brocco, Marcela Adriana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina
description Chronic stress can trigger several pathologies including mood disorders for which no clear diagnostic molecular markers have been established yet. Attractive biomarker sources are extracellular vesicles (EVs). Evs are released by cells in health and disease and contain genetic material, proteins and lipids characteristic of the cell state. Here we show that Evs recovered from the blood of animals exposed to a repeated interrupted stress protocol (RIS) have a different protein profile compared to those obtained from control animals. Proteomic analysis indicated that proteins differentially present in bulk serum Evs from stressed animals were implicated in metabolic and inflammatory pathways and several of them were previously related to psychiatric disorders. Interestingly, these serum Evs carry brain-enriched proteins including the stress-responsive neuronal protein M6a. Then, we used an in-utero electroporation strategy to selectively overexpress M6a-GFP in brain neurons and found that M6a-GFP could also be detected in bulk serum Evs suggesting a neuronal origin. Finally, to determine if these Evs could have functional consequences, we administered Evs from control and RIS animals intranasally to naïve mice. Animals receiving stress EVs showed changes in behavior and brain M6a levels similar to those observed in physically stressed animals. Such changes could therefore be attributed, or at least in part, to EV protein transfer. Altogether these findings show that EVs may participate in stress signaling and propose proteins carried by EVs as a valuable source of biomarkers for stress-induced diseases.
publishDate 2024
dc.date.none.fl_str_mv 2024-08
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/11336/266524
Monteleone, Melisa Carolina; Billi, Silvia Cristina; Abarzúa Catalán, Lorena; Henzi, Roberto; Fernandez, Eliana Mailen; et al.; Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice; Public Library of Science; Plos One; 19; 8; 8-2024; 1-23
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/266524
identifier_str_mv Monteleone, Melisa Carolina; Billi, Silvia Cristina; Abarzúa Catalán, Lorena; Henzi, Roberto; Fernandez, Eliana Mailen; et al.; Bulk serum extracellular vesicles from stressed mice show a distinct proteome and induce behavioral and molecular changes in naive mice; Public Library of Science; Plos One; 19; 8; 8-2024; 1-23
1932-6203
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://dx.plos.org/10.1371/journal.pone.0308976
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0308976
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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