Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30535257", "kind": "science-record", "revision": 9, "content_hash": "sha256:1ae987b4de89c091f07684455ca7ca92c7ac916f008b956c2d505801fc0c7206", "created_at": "2026-11-01T15:40:39Z", "updated_at": "2026-11-01T22:43:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Small Extracellular Vesicles in Rat Serum Contain Astrocyte-Derived Protein Biomarkers of Repetitive Stress.", "doi": "10.1093/ijnp/pyy098", "pmid": "30535257", "authors": ["Cristóbal Gómez-Molina", "Mauricio Sandoval", "Roberto Henzi", "Juan Pablo Ramírez", "Manuel Varas-Godoy", "Alejandro Luarte", "Carlos Andres Lafourcade", "Alejandra Lopez-Verrilli", "Karl-Heinz Smalla", "Thilo Kaehne", "Ursula Wyneken"], "journal": "The international journal of neuropsychopharmacology", "year": 2019, "abstract": "BACKGROUND: Stress precipitates mood disorders, characterized by a range of symptoms present in different combinations, suggesting the existence of disease subtypes. Using an animal model, we previously described that repetitive stress via restraint or immobilization induced depressive-like behaviors in rats that were differentially reverted by a serotonin- or noradrenaline-based antidepressant drug, indicating that different neurobiological mechanisms may be involved. The forebrain astrocyte protein aldolase C, contained in small extracellular vesicles, was identified as a potential biomarker in the cerebrospinal fluid; however, its specific origin remains unknown. Here, we propose to investigate whether serum small extracellular vesicles contain a stress-specific protein cargo and whether serum aldolase C has a brain origin.\nMETHODS: We isolated and characterized serum small extracellular vesicles from rats exposed to restraint, immobilization, or no stress, and their proteomes were identified by mass spectrometry. Data available via ProteomeXchange with identifier PXD009085 were validated, in part, by western blot. In utero electroporation was performed to study the direct transfer of recombinant aldolase C-GFP from brain cells to blood small extracellular vesicles.\nRESULTS: A differential proteome was identified among the experimental groups, including aldolase C, astrocytic glial fibrillary acidic protein, synaptophysin, and reelin. Additionally, we observed that, when expressed in the brain, aldolase C tagged with green fluorescent protein could be recovered in serum small extracellular vesicles.\nCONCLUSION: The protein cargo of serum small extracellular vesicles constitutes a valuable source of biomarkers of stress-induced diseases, including those characterized by depressive-like behaviors. Brain-to-periphery signaling mediated by a differential molecular cargo of small extracellular vesicles is a novel and challenging mechanism by which the brain might communicate health and disease states to the rest of the body.", "claims": [{"id": "claim-method", "statement": "Semiquantitative analysis of western blots was evaluated by comparing the relative optic densities of bands (fold change of stress over no stress) after restraint and immobilization using the Mann-Whitney test. In turn, the significant differences in each dataset, with a hypothetical value of 1 (no change), were assessed with a Wilcoxon-signed rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30535257", "locator": "sections[16] \"Statistical Analysis\" paragraph 2", "quote": "Semiquantitative analysis of western blots was evaluated by comparing the relative optic densities of bands (fold change of stress over no stress) after restraint and immobilization using the Mann-Whitney test. In turn, the significant differences in each dataset, with a hypothetical value of 1 (no change), were assessed with a Wilcoxon-signed rank test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The MS proteomics data obtained in this study have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD009085 (Vizcaino et al., 2016). 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The ProteomeXchange dataset has been made public via the PRIDE database, with the following details: ProteomeXchange title: rat serum exosomes after restriction stress, ProteomeXchange accession: PXD009085, PubMed ID: Not applicable, Publication DOI: Not applicable, Project Webpage: http://www.ebi.ac.uk/pride/archive/projects/PXD009085, FTP Download: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/12/PXD009085."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30535257"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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