Astrocytes and NG2-glia: what's in a name?

Abstract

Classic studies recognize two functionally segregated macroglial cell types in the central nervous system (CNS), namely astrocytes and oligodendrocytes. A third macroglial cell type has now been identified by its specific expression of the NG2 chondroitin sulphate proteoglycan (NG2-glia). These NG2-glia exist abundantly in both grey and white matter of the mature CNS and are almost as numerous as astrocytes. It is well established that NG2-glia give rise to oligodendrocytes. However, the majority of NG2-glia in the adult CNS proliferate very slowly and are non-motile. Both astrocytes and NG2-glia display a stellate morphology and express ion channels and receptors to neurotransmitters used by neurons. Both types of glia make intimate contacts with neurons in grey and white matter, and their functional differences and similarities are only beginning to be unravelled. Recent observations emphasize the need to examine the relationship between astrocytes and NG2-glia, and address the question of whether they represent overlapping or two distinct glial cell populations. To be of any relevance, this classification must relate to specific functions in the neural network. At present, the balance of evidence is that NG2-glia and astrocytes are functionally segregated populations.

Fig. 1

Detection of astrocytes and NG2-glia by different methods. (A,B) Confocal images of astrocytes (A) and NG2-glia (B) in the adult mouse cerebral cortex detected with antibodies to GFAP (A) and NG2 (B) showing multiprocessed morphology. Short arrows indicate the position of glia limitans and the pial surface. Arrowheads indicate a blood vessel. Long arrows indicate examples of positively stained cells. GFAP⁺ astrocytes extend end-feet onto the pial surface and blood vessels but NG2 cells do not. (C,D) Confocal images of astrocytes and NG2 cells in neocortex of adult transgenic mice showing differences in process arborization between astrocytes and NG2-glia. (C) EGFP fluorescence in a transgenic mouse in which EGFP is expressed in weakly GFAP⁺ protoplasmic astrocytes. (D) DsRed fluorescence in a transgenic mouse generated by injecting linearized BAC DNA containing the entire NG2 gene with DsRed inserted into the first exon. Scale bars, 20 µm.

Fig. 2

The relationship between astrocytes and NG2-glia. Both models recognize two clearly distinct populations of cells: (1) astrocytes that contain GFAP and have glutamate transporters but not AMPA receptor functions (yellow) and (2) NG2-glia that do not contain GFAP or glutamate transporters but have AMPA receptors (blue). Model A includes an additional group of cells with a phenotype intermediate between astrocytes and NG2-glia. Model B represents two segregated glial cell populations with no overlap. Most currently available data support model B rather than A, but the nomenclature ‘astrocytes’ has been used broadly in some studies to refer to cells with the NG2-glial phenotype.