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Cited by 23Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchPhagocytosis and Immune Regulation

Synaptic pruning by microglia: lessons from genetic studies in mice

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de Deus, Junia Lara, Faborode, Oluwaseun Samuel, Nandi, Sayan·2024·Developmental Neuroscience
DOI 10.1159/000541379PMC PMC12500284
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Abstract

Background: Neural circuits are subjected to refinement throughout life. The dynamic addition and elimination (pruning) of synapses are necessary for maturation of neural circuits and synaptic plasticity. Due to their phagocytic nature, microglia have been considered as the primary mediators of synaptic pruning. Synaptic pruning can strengthen an active synapse by removing excess weaker synapses during development. Inappropriate synaptic pruning can often influence a disease outcome or an injury response. Summary: This review offers a focused discussion on microglial roles in synaptic pruning, based on the evidence gathered from genetic manipulations in mice. Genetically labeled microglia and synapses often allow assessment of their interactions in real time. Further manipulations involving synaptically localized molecules, neuronally or glial-derived diffusible factors, and their respective cognate receptors in microglia provide critical evidence in support of a direct role of microglia in synaptic pruning. Key Message: We discuss microglial contact-dependent “eat-me,” “don’t-eat-me,” and “find-me” signals, as well as recently identified noncontact pruning, under the contexts of neural circuit, brain region, developmental window, and an injury or a disease state.

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  • This provides a plausible link between EDC-induced neuroinflammation and large-scale disturbances in connectivity and plasticity.

    “This provides a plausible link between EDC-induced neuroinflammation and large-scale disturbances in connectivity and plasticity (Lara de Deus et al., 2025; Yang et al., 2025).”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Lara de Deus et al., 2025

    The Introduction (page unavailable) links aberrant microglial pruning to neural-circuit and disease outcomes, and the “Find-Me” Signals section reports changes in synaptic plasticity under pathological conditions. These passages support a plausible microglial route to altered connectivity and plasticity, but the paper does not establish the proposed link from EDC-induced neuroinflammation or demonstrate large-scale disturbances caused by EDCs. (LLM, conf=0.82)

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  • Microglia are essential for synaptic pruning and circuit refinement during development, but chronic inflammatory activation can shift them toward maladaptive synapse elimination and aberrant remodeling.

    “Microglia are essential for synaptic pruning and circuit refinement during development, but chronic inflammatory activation can shift them toward maladaptive synapse elimination and aberrant remodeling.”

    From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Lara de Deus et al., 2025

    The Background and Introduction describe microglia as major mediators of developmental synaptic pruning and report aberrant activity alongside excessive pruning in a Down syndrome mouse model. The “Find-Me” Signals > Fractalkine section links early-life inflammation to later stress-induced pruning, but it does not establish the claimed shift caused by chronic inflammatory activation. The Introduction also notes that other glial cells can prune synapses, so calling microglia essential is stronger than the review’s general conclusion. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
de Deus, J. L., Faborode, O. S., & Nandi, S.
Affiliations
Howard University (US)
Corresponding author
Nandi, Sayan
ORCID
Venue
Developmental Neuroscience
Publisher
S. Karger AG
Published
2024-09-12
Volume
47
Issue
5
Pages
362-382
ISSN
  • 0378-5866 (ISSN-L)
  • 1421-9859
DOI
10.1159/000541379
PMC
PMC12500284
OpenAlex
W4402478526
Cited by
23
References
27
Citations by year
2026: 18 · 2025: 5
FWCI
1.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Developmental Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
Funders
  • National Institute of Mental Health (R21MH124294)
  • National Institute of Neurological Disorders and Stroke (R21NS116480)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Keywords
synaptic pruning, microglia, neural circuit refinement, synaptic plasticity, eat-me signals, don't eat me signal, find-me signals, neuroinflammation, genetic mouse models
MeSH terms
Animals, Brain, Neuronal Plasticity, Synapses, Microglia, Mice

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