Role of NG2 expressing cells in addiction: a new approach for an old problem

Abstract

Neuron-glial antigen 2 (NG2) is a proteoglycan expressed predominantly in oligodendrocyte progenitor cells (OPCs). NG2-expressing OPCs (NG2-OPCs) are self-renewing cells that are widely distributed in the gray and white matter areas of the central nervous system. NG2-OPCs can mature into premyelinating oligodendrocytes and myelinating oligodendroglia which serve as the primary source of myelin in the brain. This review characterizes NG2-OPCs in brain structure and function, conceptualizes the role of NG2-OPCs in brain regions associated with negative reinforcement and relapse to drug seeking and discusses how NG2-OPCs are regulated by neuromodulators linked to motivational withdrawal. We hope to provide the readers with an overview of the role of NG2-OPCs in brain structure and function in the context of negative affect state in substance abuse disorders and to integrate our current understanding of the physiological significance of the NG2-OPCs in the adult brain.

Keywords: BrdU; NG2; amygdala; hippocampus; prefrontal cortex; progenitors.

FIGURE 1

Cell cycle time for NG2-OPCs in the rodent brain at different postnatal (P) ages. The cell cycle has been found to slow down with age, and this effect has been reported in the cortex as well as corpus callosum (Psachoulia et al., 2009; Simon et al., 2011). Age in days post-partum; cell cycle time in days (d).

FIGURE 2

(A) Coronal section of the adult rat brain through the mPFC; the mPFC is shaded in peach. Proliferating cells in the mPFC differentiate into oligodendrocyte progenitor cells (OPC) and premyelinating oligodendrocytes. (B) Developmental stages of oligodendrocyte progenitors in the mPFC; proteins and transcription factors that are expressed in distinct stages are indicated below.

FIGURE 3

(A) NG2 positive (NG2+) cells are the predominant proliferating cell type in most brain regions except in the granule cell layer (GCL) of the hippocampus. Data derived from previous publications (Dawson et al., 2003; Wennstrom et al., 2004; Orre et al., 2009; Hattiangady and Shetty, 2010; Ehninger et al., 2011). (B) Survival/persistence of NG2+ cells is low in the GCL of the hippocampus. In contrast more than 50% of the surviving BrdU cells are NG2+ in the hippocampal non-GCL areas, cerebral cortex and prefrontal cortex (PFC) as well as the amygdala. Data derived from previous publications (Wennstrom et al., 2004; Komitova et al., 2006; Czeh et al., 2007; Mandyam et al., 2007; Orre et al., 2009; Hattiangady and Shetty, 2010; Ehninger et al., 2011). GCL, granule cell layer; H-GCL, hippocampus without GCL; CeC, cerebral cortex; PFC, prefrontal cortex; Amg, amygdala; CC, corpus callosum.