Evidence map›Paper›PMID 41397032›Full record

ArticleJournal of extracellular vesicles2025

Microglial Extracellular Vesicles Mediate C1q Deposition at the Pre-Synapse and Promote Synaptic Pruning.

Giulia D'Arrigo, Giulia Cutugno, Maria Teresa Golia, Francesca Sironi, Marta Lombardi, Sara Francesca Colombo, Roberto Frigerio, Marina Cretich, Paola Gagni, Elisabetta Battocchio and 9 more

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Giulia D'ArrigoInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0003-3984-8888
Giulia CutugnoInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0009-0005-2142-6929
Maria Teresa GoliaInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0002-8610-696X
Francesca SironiResearch Center for ALS, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.ORCID https://orcid.org/0000-0001-5287-3784
Marta LombardiInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0001-6703-7121
Sara Francesca ColomboInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0001-9714-3961
Roberto FrigerioInstitute of Chemical Science and Technologies, National Research Council of Italy, Milan, Italy.ORCID https://orcid.org/0000-0001-5855-7010
Marina CretichInstitute of Chemical Science and Technologies, National Research Council of Italy, Milan, Italy.ORCID https://orcid.org/0000-0001-8251-5275
Paola GagniInstitute of Chemical Science and Technologies, National Research Council of Italy, Milan, Italy.ORCID https://orcid.org/0000-0002-3652-6173
Elisabetta BattocchioInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0001-7431-2224
Cristiana BaroneSchool of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.ORCID https://orcid.org/0000-0001-5517-3214
Emanuele AzzoniSchool of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.ORCID https://orcid.org/0000-0002-4572-5692
Sonia BelliniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.ORCID https://orcid.org/0000-0002-6162-252X
Claudia SaracenoMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.ORCID https://orcid.org/0000-0001-8618-4282
Roberta GhidoniMolecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.ORCID https://orcid.org/0000-0002-7691-1957
Caterina BendottiResearch Center for ALS, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy.ORCID https://orcid.org/0000-0003-1055-1271
Rosa Chiara PaolicelliDepartment of Biomedical Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.ORCID https://orcid.org/0000-0001-6851-0849
Martina GabrielliInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0003-4958-541X
Claudia VerderioInstitute of Neuroscience, National Research Council of Italy, Vedano al Lambro, Italy.ORCID https://orcid.org/0000-0001-7216-5873

Funding

International Brain Research Organization ScientificgrantOCT/2022Ministero della Salute RF-2016-02361492Ministero dell'università e della Ricerca 2022-3CHCYXMinistero dell'università e della Ricerca 2022-CS9H53Regione Lombardia POR-FESR-2014-2020HUBRicercaInnovazione
6 · The paper itself

Abstract

C1q is released by microglia, localizes on weak synapses and acts as a tag for microglial synaptic pruning. However, how C1q tags synapses during the pruning period remains to be fully elucidated. Here, we report that C1q is delivered via extracellular vesicles by microglia to pre-synaptic sites that externalize phosphatidylserine. Using approaches to increase or reduce vesicles production in microglia, by C9orf72 knock out or pharmacological inhibition, respectively, we provided mechanistic evidence linking extracellular vesicle release to pre-synaptic remodelling in neuron-microglia cultures. In C9orf72 knockout mice, we confirmed larger production of microglial extracellular vesicles and showed augmented C1q presynaptic deposition associated with enhanced engulfment by microglia in the early postnatal hippocampus. Finally, we provide evidence that microglia physiologically release more vesicles during the period of postnatal circuit refinement. These findings implicate abnormal release of microglial extracellular vesicles in both neurodevelopmental and age-related disorders characterized by dysregulated microglia-mediated synaptic pruning.

Indexed as

CA1 Region, HippocampalComplement C1qExtracellular VesiclesMicrogliaNeuronal PlasticityAnimalsFemaleMaleMiceMice, KnockoutComplement C1qC1qC9orf72 knock outextracellular vesiclesmicrogliasynaptic pruning

Identifiers

PMID41397032
PMCPMC12704692

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.