Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome

Extracellular vesicles (EVs) are tiny membranous structures that mediate intercellular communication. The role(s) of these vesicles have been widely investigated in the context of neurological diseases; however, their potential implications in the neuropathology subjacent to human psychiatric disord...

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Autores: Lorca, Cristina, Fernández-Rhodes, María, Sánchez Milán, José Antonio, Mulet, Maria, Elortza, Félix, Ramos-Miguel, Alfredo, Callado, Luis F., Meana, J. Javier, Mur, Maria, Batalla, Iolanda, Vilella, Elisabet, Serra, Aida, Gallart-Palau, Xavier
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10459.1/465164
Acesso em linha:https://doi.org/10.3390/biomedicines12010129
https://hdl.handle.net/10459.1/465164
Access Level:acceso abierto
Palavra-chave:Extracellular vesicles
Molecular exchange
Neuroinflammation
Systems biology
Immunoglobulins
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network_name_str España
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dc.title.none.fl_str_mv Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
title Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
spellingShingle Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
Lorca, Cristina
Extracellular vesicles
Molecular exchange
Neuroinflammation
Systems biology
Immunoglobulins
title_short Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
title_full Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
title_fullStr Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
title_full_unstemmed Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
title_sort Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
dc.creator.none.fl_str_mv Lorca, Cristina
Fernández-Rhodes, María
Sánchez Milán, José Antonio
Mulet, Maria
Elortza, Félix
Ramos-Miguel, Alfredo
Callado, Luis F.
Meana, J. Javier
Mur, Maria
Batalla, Iolanda
Vilella, Elisabet
Serra, Aida
Gallart-Palau, Xavier
author Lorca, Cristina
author_facet Lorca, Cristina
Fernández-Rhodes, María
Sánchez Milán, José Antonio
Mulet, Maria
Elortza, Félix
Ramos-Miguel, Alfredo
Callado, Luis F.
Meana, J. Javier
Mur, Maria
Batalla, Iolanda
Vilella, Elisabet
Serra, Aida
Gallart-Palau, Xavier
author_role author
author2 Fernández-Rhodes, María
Sánchez Milán, José Antonio
Mulet, Maria
Elortza, Félix
Ramos-Miguel, Alfredo
Callado, Luis F.
Meana, J. Javier
Mur, Maria
Batalla, Iolanda
Vilella, Elisabet
Serra, Aida
Gallart-Palau, Xavier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Extracellular vesicles
Molecular exchange
Neuroinflammation
Systems biology
Immunoglobulins
topic Extracellular vesicles
Molecular exchange
Neuroinflammation
Systems biology
Immunoglobulins
description Extracellular vesicles (EVs) are tiny membranous structures that mediate intercellular communication. The role(s) of these vesicles have been widely investigated in the context of neurological diseases; however, their potential implications in the neuropathology subjacent to human psychiatric disorders remain mostly unknown. Here, by using next-generation discovery-driven proteomics, we investigate the potential role(s) of brain EVs (bEVs) in schizophrenia (SZ) by analyzing these vesicles from the three post-mortem anatomical brain regions: the prefrontal cortex (PFC), hippocampus (HC), and caudate (CAU). The results obtained indicate that bEVs from SZ-affected brains contain region-specific proteins that are associated with abnormal GABAergic and glutamatergic transmission. Similarly, these vesicles from the analyzed regions were implicated in synaptic decay, abnormal brain immunity, neuron structural imbalances, and impaired cell homeostasis. Our findings also provide evidence, for the first time, that networks of molecular exchange (involving the PFC, HC, and CAU) are potentially active and mediated by EVs in non-diseased brains. Additionally, these bEV-mediated networks seem to have become partially reversed and largely disrupted in the brains of subjects affected by SZ. Taken as a whole, these results open the door to the uncovering of new biological markers and therapeutic targets, based on the compositions of bEVs, for the benefit of patients affected by SZ and related psychotic disorders.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.3390/biomedicines12010129
https://hdl.handle.net/10459.1/465164
url https://doi.org/10.3390/biomedicines12010129
https://hdl.handle.net/10459.1/465164
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114885RB-C21
Reproducció del document publicat a https://doi.org/10.3390/biomedicines12010129
Biomedicines, 2024, vol. 12, núm. 1, 129
dc.rights.none.fl_str_mv cc-by (c) Cristina Lorca et al., 2024
Attribution 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
rights_invalid_str_mv cc-by (c) Cristina Lorca et al., 2024
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular ConnectomeLorca, CristinaFernández-Rhodes, MaríaSánchez Milán, José AntonioMulet, MariaElortza, FélixRamos-Miguel, AlfredoCallado, Luis F.Meana, J. JavierMur, MariaBatalla, IolandaVilella, ElisabetSerra, AidaGallart-Palau, XavierExtracellular vesiclesMolecular exchangeNeuroinflammationSystems biologyImmunoglobulinsExtracellular vesicles (EVs) are tiny membranous structures that mediate intercellular communication. The role(s) of these vesicles have been widely investigated in the context of neurological diseases; however, their potential implications in the neuropathology subjacent to human psychiatric disorders remain mostly unknown. Here, by using next-generation discovery-driven proteomics, we investigate the potential role(s) of brain EVs (bEVs) in schizophrenia (SZ) by analyzing these vesicles from the three post-mortem anatomical brain regions: the prefrontal cortex (PFC), hippocampus (HC), and caudate (CAU). The results obtained indicate that bEVs from SZ-affected brains contain region-specific proteins that are associated with abnormal GABAergic and glutamatergic transmission. Similarly, these vesicles from the analyzed regions were implicated in synaptic decay, abnormal brain immunity, neuron structural imbalances, and impaired cell homeostasis. Our findings also provide evidence, for the first time, that networks of molecular exchange (involving the PFC, HC, and CAU) are potentially active and mediated by EVs in non-diseased brains. Additionally, these bEV-mediated networks seem to have become partially reversed and largely disrupted in the brains of subjects affected by SZ. Taken as a whole, these results open the door to the uncovering of new biological markers and therapeutic targets, based on the compositions of bEVs, for the benefit of patients affected by SZ and related psychotic disorders.: Support for this work was provided by the National Institute of Health/Instituto de Salud Carlos III-ISCIII, Spain (PI22/00443 to X.G.-P.) (grant co-funded by the European Union); the Ministry of Science and Innovation-MCIN, Spain and the National Research Council/Agencia Estatal de Investigación-AEI, Spain (PID2020-114885RB-C21 to A.S.) funded by MCIN/AEI/10.13039/501100011033. This research was also co-financed by the Spanish Ministry of Science and Innovation with funds from the European Union NextGenerationEU; from the Recovery, Transformation and Resilience Plan (PRTR-C17.I1); and from the Autonomous Community of Catalonia within the framework of the Biotechnology Plan Applied to Health ((EVBRAINTARGET-Y7340-ACPPCCOL007 to X.G.-P., A.S., M.Mur, and A.R.-M.) coordinated by the Institute for Bioengineering of Catalonia (IBEC)); the Diputació de Lleida, Spain (PIRS22/03 to X.G.-P. & I.B. and PIRS23/02 to A.S.); the Catalan Research Council-AGAUR (AGAUR 21SGR010065 to E.V.; 2023 LLAV 00056 to X.G.-P.; and 2022 DI 100 to X.G.-P.); and the Basque Government (IT211/19 and IT1512/22 to J.J.M and L.F.C.). X.G.- P. acknowledges a Miguel Servet program tenure track contract (CP21/00096) from the ISCIII, awarded on the 2021 call under the Health Strategy Action, co-funded by the European Union (FSE+). A.S. acknowledges a Ramón y Cajal program tenure track contract (RYC2021-030946-I) funded by MCIN/AEI/10.13039/501100011033 and by the “European Union NextGenerationEU/PRTR”; A.R.-M. acknowledges a Ramón y Cajal program tenure track contract (RYC-2016-19282) funded by MCIN/AEI/10.13039/501100011033. M.F.-R.’s postdoctoral contract is funded by PRTR-C17.I1 and EVBRAINTARGET-Y7340-ACPPCCOL007. C.L.’s PhD is funded by the European Social Fund for the recruitment of predoctoral researchers (PEJD-2019-PRE/BIO-16475); M.M.’s PhD is funded by the MCIN-AEI (PR2021-097934); and J.A.S.M.’s PhD is funded by AGAUR (2023 FI-1 00054), and J.A.S.M.’s contributions were also supported by Diputació de Lleida ‘Ajuts al Talent en Investigació Biomèdica”. IRBLLEIDA, J.A.S.M., X.G.-P., and A.S. are co-funded by the CERCA Program/Generalitat de Catalunya. J.J.M., A.R.-M., and X.G.-P. are members of the ExoPsyCog Consortium, funded by IKUR-Neurobiosciences—Basque Government.MDPI2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://doi.org/10.3390/biomedicines12010129https://hdl.handle.net/10459.1/465164reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglésinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114885RB-C21Reproducció del document publicat a https://doi.org/10.3390/biomedicines12010129Biomedicines, 2024, vol. 12, núm. 1, 129cc-by (c) Cristina Lorca et al., 2024Attribution 4.0 Internationalinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/oai:recercat.cat:10459.1/4651642026-05-29T05:05:01Z
score 15,81155

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