A review of functional heterogeneity among astrocytes and the CS56-specific antibody-mediated detection of a subpopulation of astrocytes in adult brains

Astrocytes comprise the largest class of glial cells in the mammalian central nerve system (CNS). Although astrocytes were long considered to be a homogeneous population of neuron-supporting cells, recent decades have seen a shift toward the recognition that astrocytes exhibit morphological and functional heterogeneities and serve as essential modulators of brain functions. However, the mechanism underlying astrocyte diversity remains unclear, and the different subpopulations are difficult to identify due to a lack of specific cell markers. In this review, I discuss current knowledge regarding astrocyte heterogeneity and introduce a subpopulation that can be detected via labeling with a chondroitin sulfate-specific antibody (CS56). These CS56-positive astrocytes were found to selectively express tenascin-R (TNR) in the adult mouse cerebral cortex. Further research demonstrated significantly lower levels of glutamate uptake activity and glutamate aspartate transporter expression in TNR-knockdown astrocytes relative to controls, suggesting that the expression and secretion of Tnr by a subpopulation of astrocytes may contribute to region-specific neuron–astrocyte interactions. In summary, these results suggest that CS56-specific antibody and Tnr could be used as novel markers to detect an astrocyte subpopulation in the adult CNS.