Review Article | Published:

A stocked toolbox for understanding the role of astrocytes in disease

Nature Reviews Neurologyvolume 14pages351362 (2018) | Download Citation

Abstract

Our understanding of astrocytes and their role in neurological diseases has increased considerably over the past two decades as the diverse roles of these cells have become recognized. Our evolving understanding of these cells suggests that they are more than support cells for neurons and that they play important roles in CNS homeostasis under normal conditions, in neuroprotection and in disease exacerbation. These multiple functions make them excellent candidates for targeted therapies to treat neurological disorders. New technological advances, including in vivo imaging, optogenetics and chemogenetics, have allowed us to examine astrocytic functions in ways that have uncovered new insights into the dynamic roles of these cells. Furthermore, the use of induced pluripotent stem cell-derived astrocytes from patients with a host of neurological disorders can help to tease out the contributions of astrocytes to human disease. In this Review, we explore some of the technological advances developed over the past decade that have aided our understanding of astrocyte function. We also highlight neurological disorders in which astrocyte function or dysfunction is believed to have a role in disease pathogenesis or propagation and discuss how the technological advances have been and could be used to study each of these diseases.

Key points

  • Astrocytes not only have key homeostatic functions in the CNS but also respond to neuronal injury in both neuroprotective and pathological manners.

  • Astrocytes have key roles in a broad spectrum of neurodevelopmental and neurodegenerative diseases.

  • New tools have been developed to evaluate the structural, functional and molecular mechanisms by which astrocytes respond to injury.

  • The in vivo methods by which astrocytes can be studied have revealed new layers of complexity in astrocyte function, which could not have been appreciated with the use of older experimental approaches.

  • The use of induced pluripotent stem cell-derived astrocytes could help with interpretation of preclinical observations as they are used to direct the design of human therapeutics.

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Reviewer information

Nature Reviews Neurology thanks L. Barbeito, L. Ferraiuolo and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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  1. Johns Hopkins University, School of Medicine, Baltimore, MD, USA

    • Akshata Almad
    •  & Nicholas J. Maragakis

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Both authors contributed to all aspects of manuscript preparation.

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The authors declare no competing interests.

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Correspondence to Nicholas J. Maragakis.

Glossary

Tripartite synapse

A site at which three-way communication occurs between presynaptic, postsynaptic and astrocytic processes during synaptic transmission.

Gliotransmission

The release of glutamate, ATP, d-serine and other neurotransmitters that are essential for synaptic transmission and plasticity from astrocytes.

Microdialysis

A minimally invasive method of sampling in vivo concentrations of various analytes (neurotransmitters, peptides, glutamate, etc.) in the brain and spinal cord using a dialysis probe.

Single-wavelength glutamate sensor

A fluorescent sensor based on a circularly permuted single fluorophore rather than Förster resonance energy transfer (FRET), which is based on ratiometric measurements at two different wavelengths.

Human cortical spheroids

(hCSs). 3D cultures that produce laminated cerebral cortex-like structures that include astrocytes as part of a cortical neuronal circuit.

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https://doi.org/10.1038/s41582-018-0010-2