Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter

Abstract

The NG2 antibody, which recognises an integral membrane chondroitin sulphate, labels a significant population of cells in adult CNS white matter tracts of the rat optic nerve and anterior medullary velum (AMV). Adult NG2+ cells are highly complex with multiple branching processes and we show by EM immunocytochemistry that they extend perinodal processes, which contact nodes of Ranvier. NG2+ cells do not react to conventional immunohistochemical markers for adult glia and so we reservedly term them NG2P cells. In vitro, NG2 labels oligodendrocyte-type-2 astrocyte (O-2A) progenitors that can give rise to oligodendrocytes or type-2 astrocytes, depending on the culture medium. Thus, it is possible that NG2P cells may be derived from the same stem cells as oligodendrocytes. Interestingly, NG2+ cells identified previously in adult CNS displayed phenotypic characteristics of O-2Aadult progenitors and it is possible that, like them, NG2P cells might retain the capacity of generating oligodendrocytes in the adult CNS. This may be an important role of NG2P cells in demyelinating diseases such as multiple sclerosis. It is significant therefore that the perinodal processes of NG2P cells contact the only sites of exposed axolemma in myelinated axons, so that NG2P cells are ideally situated to detect and respond to changes in axonal function during demyelination. A further implication of our finding is that NG2P cells may perform functions at nodes of Ranvier previously attributed to perinodal astrocytes, including the clustering and maintenance of sodium channels in the axon membrane at nodes, during development and following demyelination.

Morphological and physiological interactions of NG2‐glia with astrocytes and neurons

“…Adult NG2‐glia in vivo are probably equivalent to the O‐2A cells isolated from adult CNS by ffrench‐Constant & Raff (1986), which can be driven in vitro to generate oligodendrocytes and astrocytes; Fulton et al. (1992) identified adult O‐2A cells in vivo in the optic nerve using cobalt uptake through AMPA‐type glutamate receptors and these are morphologically identical to NG2‐glia subsequently described in the optic nerve (Butt et al. 1999).…”

“… NG2‐glia and astroglia visualized in two different transgenic mouse lines. Following fixation in 4% paraformaldehyde, brains from NG2‐DsRed mice (A,B) and GFAP‐EGFP mice (C,D), aged postnatal day (P)15–30, mid‐sagital sections were cut at 50 µm on a vibratome and immunolabelled for either NG2 (A,B) or GFAP (C,D), using immunohistochemistry protocols described previously (Butt et al. 1999).…”

“…Astrocytes and NG2‐glia both contact nodes of Ranvier, the sites of action potential propagation and only areas of axolemma not covered by myelin in the optic nerve, and therefore the site for direct signalling from axons to astrocytes and NG2‐glia (Butt et al. 1994, 1999). In addition, vesicular release of glutamate from unmyelinated axons has been shown to evoke AMPA receptor‐mediated currents in NG2‐glia (Ziskin et al.…”

“…This is the functional substrate by which astroglia may serve as active partners to neurons in information processing and integration. Recent studies show that NG2‐glia also contact synapses and nodes of Ranvier, and respond to neuronally released neurotransmitters (Butt et al. 1999; Bergles et al.…”

Oligodendrocyte Lineage Cells in Chronic Demyelination of Multiple Sclerosis Optic Nerve

“…In addition to their role as oligodendrocyte progenitors (OP) , NG2 cells have other important functions within the normal CNS, most of which involve intimate physical associations of their fine, far‐reaching processes . Therefore, such pronounced NG2 cell loss, in addition to diminishing the ability to replace oligodendroglial cells, could have adversely affected the timely differentiation of the premyOls, particularly given the suggested role of NG2 cells in the establishment of nodes .…”