Astrocyte Diversity: Current Insights and Future Directions

Abstract

Astrocytes make up 20-40% of glial cells within the central nervous system (CNS) and provide several crucial functions, ranging from metabolic and structural support to regulation of synaptogenesis and synaptic transmission. Although these cells are morphologically and functionally complex, astrocytes have been historically regarded as homogenous cell populations and studied as one population of cells. Fortunately, recent evidence in RNA profiling and imaging data has begun to refute this view. These studies suggest heterogeneity of astrocytes across brain regions, differing in many aspects such as morphology, function, physiological properties, developmental origins, and response to disease. Increased understanding of astrocyte heterogeneity is critical for investigations into the function of astrocytes in the brain and neuro-glia interactions. Furthermore, insights into astrocyte heterogeneity can help better understand their role in neurological disorders and potentially produce novel approaches to treating these diseases.

Keywords: Astrocyte; Astrocyte diversity; Astrocyte heterogeneity; Development; Function; Morphology; Neurodegeneration; Neurological disorder.

Figure 1.

Early morphological discoveries in neurons and astrocyte demonstrate morphological diversity in both cell types. A. Diversity of neuronal cells. a, Purkinjie neuron (human); b, pyramidal neuron (rabbit); c, motor neuron (cat); d,e horizontal neuron (cat); f, pre-motor interneuron (locust); g, visual amacrinal neuron (fly); h, multipolar neuron (fly); i, visual monopolar neuron (fly); j, visual interneuron (locust); k, pre-motor interneuron (crayfish); l, mechanical sensory neuron (cray fish); (from Cajal, Fisher and Boycott, Burrows, Strausfeld, O’Shea, Rowell and Reichert). Illustration taken from H. Reichert; Neurobiolgie, page 23 [9]. B. Golgi staining of astrocytes in human cerebellum by Ramon y Cajal showing diversity of astrocytes. b, Bergmann glia; s, smooth protoplasmic astrocytes; v, velate astrocytes; f, fibrous astrocytes. Reproduced with permission from Springer Science & Business media: H. Kimelberg; Astrocytes in (patho)physiology of the nervous system, astrocyte heterogeneity or homogeneity? page 3 [10].