Neuron-NG2 Cell Synapses: Novel Functions for Regulating NG2 Cell Proliferation and Differentiation

Abstract

NG2 cells are a population of CNS cells that are distinct from neurons, mature oligodendrocytes, astrocytes, and microglia. These cells can be identified by their NG2 proteoglycan expression. NG2 cells have a highly branched morphology, with abundant processes radiating from the cell body, and express a complex set of voltage-gated channels, AMPA/kainate, and GABA receptors. Neurons notably form classical and nonclassical synapses with NG2 cells, which have varied characteristics and functions. Neuron-NG2 cell synapses could fine-tune NG2 cell activities, including the NG2 cell cycle, differentiation, migration, and myelination, and may be a novel potential therapeutic target for NG2 cell-related diseases, such as hypoxia-ischemia injury and periventricular leukomalacia. Furthermore, neuron-NG2 cell synapses may be correlated with the plasticity of CNS in adulthood with the synaptic contacts passing onto their progenies during proliferation, and synaptic contacts decrease rapidly upon NG2 cell differentiation. In this review, we highlight the characteristics of classical and nonclassical neuron-NG2 cell synapses, the potential functions, and the fate of synaptic contacts during proliferation and differentiation, with the emphasis on the regulation of the NG2 cell cycle by neuron-NG2 cell synapses and their potential underlying mechanisms.

Changes in the proliferative capacity of NG2 cell subpopulations during postnatal development of the mouse hippocampus

“…On the one hand side, the S100b protein in astroglia impacts neuronal neurite outgrowth (Azmitia et al 1990;Liu and Lauder 1992) and may influence synaptic activity (Nishiyama et al 2002b). On the other hand side, NG2 glia form synapses with neurons , and synapses influence the fate of NG2 glia (Yang et al 2013). These results suggest that expression of S100b by NG2 glia may play a pivotal role in the formation and modulation of synapses between NG2 glia and neurons.…”

Juvenile striatal white matter is resistant to ischemia‐induced damage

“…OPCs are the most proliferative cell in the brain and are evenly distributed throughout brain parenchyma (Nishiyama et al, ). OPCs have traditionally been viewed with regard to their ability to respond to demyelination and they differentiate into new myelin‐forming oligodendrocytes after injury, but it is becoming increasingly obvious that they have much more diverse functions both in healthy and injured brain tissue (Hughes et al, ; Xu et al, ; Yang et al, ). In this light, OPCs are more accurately labeled as NG2‐cells (or NG2‐glia) based on their expression of the NG2 proteoglycan and their distinct functionality (Nishiyama et al, ).…”

Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?

“…In addition, prolonged exposure of OPCs and Oli‐neu cells to AMPAR agonists is known to trigger downregulation of AMPAR subunits, particularly those which render AMPARs Ca 2+ ‐permeable (Begum et al, ; Hossain, Liu, Fragoso, & Almazan, ; Jourdi et al, ; Mangiavacchi & Wolf, ). Therefore, decrease in proliferation and lineage progression of OPCs upon prolonged exposure to AMPAR agonists observed in vitro may be mediated by reduced entry of Ca 2+ which is a key regulator of proliferation and differentiation (Hamilton, Hubbard, & Butt, ; Toth, Shum, & Prakriya, ; Yang, Xiong, & Yao, ). Remarkably, Ca 2+ ‐entry into OPCs may be decreased even if Ca 2+ ‐impermeable AMPARs get down‐regulated because this would prevent opening of L‐type VGCCs which is triggered upon AMPAR‐mediated depolarization (Sun et al, ).…”