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Do glia drive synaptic and cognitive impairment in disease?

Nature Neuroscience volume 18, pages 1539–1545 (2015)Cite this article

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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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Figure 1: Astrocytes and microglia interacting with synapses.

Debbie Maizels/Nature Publishing Group

Figure 2: Astrocyte and microglia regulation of synaptic formation, function and elimination, and potential implications for disease.

Debbie Maizels/Nature Publishing Group

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Acknowledgements

We thank L. Sun, J. Wallace and V. Murthy for providing the images used in Figure 1. We also thank S. Hong and E. Lehrman for helpful discussions and critical reading of the manuscript.

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  1. Won-Suk Chung and Christina A Welsh: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neurobiology, Stanford University, School of Medicine, Palo Alto, California, USA

    Won-Suk Chung & Ben A Barres

  2. Department of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Christina A Welsh & Beth Stevens

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  1. Won-Suk Chung
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  2. Christina A Welsh
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Correspondence to Beth Stevens.

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Competing interests

B.A.B. is a co-founder of Annexon Biosciences, Inc., a company making new drugs to treat neurological disorders, and B.S. is on the scientific advisory board of Annexon Biosciences.

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Chung, WS., Welsh, C., Barres, B. et al. Do glia drive synaptic and cognitive impairment in disease?. Nat Neurosci 18, 1539–1545 (2015). https://doi.org/10.1038/nn.4142

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