Phenotypic heterogeneity of astrocytes in motor neuron disease

Abstract

Accumulating evidence has shown that astrocytes do not just support the function of neurons, but play key roles in maintaining the brain environment in health and disease. Contrary to the traditional understanding of astrocytes as static cells, reactive astrocytes possess more diverse functions and phenotypes than previously predicted. In the present focused review, we summarize the evidence showing that astrocytes are playing profound roles in the disease process of amyotrophic lateral sclerosis. Aberrantly activated astrocytes in amyotrophic lateral sclerosis rodents express microglial molecular markers and provoke toxicities to accelerate disease progression. In addition, TIR domain-containing adapter protein-inducing interferon-β-dependent innate immune pathway in astrocytes also has a novel function in terminating glial activation and neuroinflammation. Furthermore, heterogeneity in phenotypes and functions of astrocytes are also observed in various disease conditions, such as other neurodegenerative diseases, ischemia, aging and acute lesions in the central nervous system. Through accumulating knowledge of the phenotypic and functional diversity of astrocytes, these cells will become more attractive therapeutic targets for neurological diseases.

Keywords: amyotrophic lateral sclerosis; astrocyte; neurodegeneration; neuroinflammation; phenotype.

Figure 1

Features of aberrantly activated astrocytes. (a) Representative confocal images of spinal cord astrocytes from wild‐type and symptomatic superoxide dismutase 1 (SOD1)^G93A rats stained for GFAP (green) and CD206 (red). (b) Representative confocal images of spinal cord astrocytes from wild‐type and end‐stage SOD1^G93A mice stained for GFAP (green), Mac‐2 (red) and DAPI (blue). Note that aberrantly activated astrocytes show a large round cell body with shorter processes. Scale bars, 10 μm.