Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome
dc.contributor.author | Lorca, Cristina | |
dc.contributor.author | Fernández Rhodes, María | |
dc.contributor.author | Sánchez Milán, Jose Antonio | |
dc.contributor.author | Mulet, María | |
dc.contributor.author | Elortza, Felix | |
dc.contributor.author | Ramos Miguel, Alfredo | |
dc.contributor.author | Callado Hernando, Luis Felipe | |
dc.contributor.author | Meana Martínez, José Javier | |
dc.contributor.author | Mur, Maria | |
dc.contributor.author | Batalla, Iolanda | |
dc.contributor.author | Vilella, Elisabet | |
dc.contributor.author | Serra, Aida | |
dc.contributor.author | Gallart Palau, Xavier | |
dc.date.accessioned | 2024-02-07T15:08:32Z | |
dc.date.available | 2024-02-07T15:08:32Z | |
dc.date.issued | 2024-01-08 | |
dc.identifier.citation | Biomedicines 12(1) : (2024) // Article ID 129 | es_ES |
dc.identifier.issn | 2227-9059 | |
dc.identifier.uri | http://hdl.handle.net/10810/64733 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | 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. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2020-114885RB-C21 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/RYC2021-030946-I | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/RYC-2016-19282 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PR2021-097934 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/es/ | |
dc.subject | extracellular vesicles | es_ES |
dc.subject | molecular exchange | es_ES |
dc.subject | neuroinflammation | es_ES |
dc.subject | systems biology | es_ES |
dc.subject | immunoglobulins | es_ES |
dc.subject | brain antibodies | es_ES |
dc.subject | psychiatry | es_ES |
dc.subject | psychotic spectrum | es_ES |
dc.title | Next-Generation Proteomics of Brain Extracellular Vesicles in Schizophrenia Provide New Clues on the Altered Molecular Connectome | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2024-01-26T14:10:57Z | |
dc.rights.holder | © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2227-9059/12/1/129 | es_ES |
dc.identifier.doi | 10.3390/biomedicines12010129 | |
dc.departamentoes | Farmacología | |
dc.departamentoeu | Farmakologia |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's license is described as © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/ 4.0/).