Abstract
NG2-expressing parenchymal precursors (NG2+p) serve as primary source of myelinating oligodendrocytes in both the developing and adult Central Nervous System (CNS). However, their abundance, limited differentiation potential at adult stages along with stereotypic reaction to injury independent of the extent of myelin loss suggest that NG2+p exert functions additional to myelin production. In support of this view, NG2+p express a complex battery of molecules known to exert neuromodulatory and neuroprotective functions. Further, they establish intimate physical associations with the other CNS cell types, receive functional synaptic contacts and possess ion channels apt to constantly sense the electrical activity of surrounding neurons. These latter features could endow NG2+p with the capability to affect neuronal functions with potential homeostatic outcomes. Here we summarize and discuss current evidence favoring the view that NG2+p can participate in circuit formation, modulate neuronal activity and survival in the healthy and injured CNS, and propose perspectives for studies that may complete our understanding of NG2+p roles in physiology and pathology.
Highlights
During Central Nervous System (CNS) ontogenesis, myelinating oligodendrocytes originate from highly ramified neural precursors expressing the platelet-derived growth factor alpha receptor (PDGFRa) and the NG2 chondroitin sulfate proteoglycan (Zhu et al, 2008a,b)
We will refer to these cells as NG2expressing precursors (NG2+p), NG2 is expressed by pericytes of the vasculature (Stallcup, 2002) and reported in astrocyte subsets (Matthias et al, 2003)
Previous experiments at later developmental stages have shown that myelin formation shapes cerebellar connections by removing exuberant collateral branches of Purkinje neurons (Gianola et al, 2003). These results suggest that cycling NG2+p participate in shaping cerebellar circuits well before myelination starts
Summary
During Central Nervous System (CNS) ontogenesis, myelinating oligodendrocytes originate from highly ramified neural precursors expressing the platelet-derived growth factor alpha receptor (PDGFRa) and the NG2 chondroitin sulfate proteoglycan (Zhu et al, 2008a,b). The persistence of a large pool of quiescent (i.e., neither engaged in proliferation nor maturation) NG2+p with limited differentiation potential at adult ages has suggested that these cells do represent a transitional stage along the oligodendroglial lineage, but rather a novel type of glia endowed with specific properties and functions (Nishiyama et al, 2002).
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