Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Frontiers in Cellular Neuroscience, 2021 · DOI: 10.3389/fncel.2021.703810 · Published: July 26, 2021

Simple Explanation

Astrocytes, vital for CNS health, react to injuries through "reactive astrogliosis". This response varies across conditions like stroke and demyelination. This review explores whether this variation reflects distinct astrocyte types (heterogeneity) or adaptable responses within astrocyte subsets (plasticity). Understanding this distinction is crucial for developing effective therapies targeting astrocytes after CNS injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Astrocyte diversity is observed in various CNS pathologies, including ischemic stroke, demyelination, and traumatic injury, but the extent to which this diversity represents heterogeneity or plasticity remains unclear.
2
The majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity.
3
Distinguishing between astrocyte heterogeneity and plasticity is essential for directing our understanding of reactive astrogliosis and informing potential treatments.

Research Summary

Astrocytes are critical for CNS functioning in health and disease, exhibiting significant variation across temporal, topographical, sex, and age-related variables. Reactive astrogliosis, the process by which astrocytes change in response to pathology, was once viewed as homogenous but is now recognized as remarkably diverse. The review suggests that much of astrocyte diversity in CNS pathologies represents plasticity, highlighting key limitations in current knowledge and suggesting future research areas.

Practical Implications

Therapeutic Development

Understanding astrocyte diversity is critical for guiding therapeutic development, enabling targeted interventions aimed at manipulating aberrant and/or pro-pathogenic responses.

Disease Pathogenesis

Understanding the contributions of plasticity versus heterogeneity to observed astrocyte diversity provides important considerations for the understanding of disease pathogenesis.

Targeted Interventions

Recognition of the contributions of plasticity has the potential to reveal novel targets amendable to extrinsic manipulation via targeted therapeutic approaches across multiple aspects of disease pathology.

Study Limitations

1
Limited functional data corroborating astrocyte diversity.
2
Limited fate-mapping data on astrocyte subsets in the adult CNS.
3
A relative paucity of scRNA-seq studies characterizing astrocyte diversity in models of CNS trauma, as compared to demyelination and ischemic stroke.

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