Cited by 385Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchNeurological Disease Mechanisms and Treatments

Do glia drive synaptic and cognitive impairment in disease?

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Chung, Won-Suk, Welsh, Christina A, Barres, Ben A, Stevens, Beth·2015·Nature Neuroscience

Abstract

Synaptic dysfunction is a hallmark of many neurodegenerative and psychiatric brain disorders, yet we know little about the mechanisms that underlie synaptic vulnerability. Although neuroinflammation and reactive gliosis are prominent in virtually every CNS disease, glia are largely viewed as passive responders to neuronal damage rather than drivers of synaptic dysfunction. This perspective is changing with the growing realization that glia actively signal with neurons and influence synaptic development, transmission and plasticity through an array of secreted and contact-dependent signals. We propose that disruptions in neuron-glia signaling contribute to synaptic and cognitive impairment in disease. Illuminating the mechanisms by which glia influence synapse function may lead to the development of new therapies and biomarkers for synaptic dysfunction.

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  • During normal brain development, microglia engulf synapses and sculpt synaptic connections via a role for complement.

    “During normal brain development, mounting evidence indicates that microglia engulf synapses and sculpt synaptic connections via a novel role for complement, a component of the innate immune system that enhances the clearance of microbes or damaged cells by phagocytes (Boulanger, 2009; Stephan et al., 2012; Chung et al., 2015).”

    From Microglia in Alzheimer’s disease (2018) · cites this paper as Chung et al., 2015

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Authors
Chung, W.-S., Welsh, C. A., Barres, B. A., & Stevens, B.
Affiliations
  • Stanford Medicine (US)
  • Boston Children's Hospital (US)
Corresponding author
Stevens, Beth
Venue
Nature Neuroscience
Published
2015-10-27
Volume
18
Issue
11
Pages
1539-1545
ISSN
  • 1097-6256 (ISSN-L)
  • 1546-1726
OpenAlex
W1876773427
Cited by
385
References
80
Citations by year
2026: 10 · 2025: 15 · 2024: 26 · 2023: 36 · 2022: 31 · 2021: 43 · 2020: 41 · 2019: 58 · 2018: 41 · 2017: 47 · 2016: 36 · 2015: 1
FWCI
3.32
Type
journal article
Language
en
Open access
Locations
  • Nature Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (T32AG000222)
  • National Institute of Neurological Disorders and Stroke (R01NS071008)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
glia, neuron-glia signaling, synaptic dysfunction, cognitive impairment, neuroinflammation, reactive gliosis, synaptic plasticity, neurodegenerative diseases, mental illness, contact-dependent signaling, biomarkers
MeSH terms
Animals, Astrocytes, Cognition Disorders, Humans, Synaptic Transmission, Neuroglia, Neuronal Plasticity, Neurons

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