Morphological characterization of NG2 glia and their association with neuroglial cells in the 3-nitropropionic acid\u2013lesioned striatum of rat

Xuyan Jin,Jeong-Heon Choi,Tae-Ryong Riew,Mun-Yong Lee,Hong Lim Kim

doi:10.1038/s41598-018-24385-0

Abstract

Our aim was to examine the spatiotemporal profiles and phenotypic characteristics of neuron-glia antigen 2 (NG2) glia and their associations with neuroglial cells in striatal lesions due to the mitochondrial toxin 3-nitropropionic acid (3-NP). In control striatum, weak NG2 immunoreactivity was restricted to resting NG2 glia with thin processes, but prominent NG2 expression was noted on activated microglia/macrophages, and reactive NG2 glia in the lesion core after 3-NP injection. Activation of NG2 glia, including enhanced proliferation and morphological changes, had a close spatiotemporal relationship with infiltration of activated microglia into the lesion core. Thick and highly branched processes of reactive NG2 glia formed a cellular network in the astrocyte-free lesion core and primarily surrounded developing cavities 2–4 weeks post-lesion. NG2 glia became associated with astrocytes in the lesion core and the border of cavities over the chronic interval of 4–8 weeks. Immunoelectron microscopy indicated that reactive NG2 glia had large euchromatic nuclei with prominent nucleoli and thick and branched processes that ramified distally. Thus, our data provide detailed information regarding the morphologies of NG2 glia in the lesion core, and support the link between transformation of NG2 glia to the reactive form and microglial activation/recruitment in response to brain insults.

Highlights

Neuron-glia antigen 2 (NG2) glia are characterized by expression of surface chondroitin sulfate proteoglycan 41–5
We examined the time course and distribution of and the cell types involved in the induction of neuronglia antigen 2 (NG2) expression in the lesioned striatum during the 8 weeks following an injection of the natural mitochondrial toxin 3-nitropropionic acid (3-NP)
Our data is in contrast with that of previous studies on ischemic brains, wherein the molecular weight of NG2 in nonischemic regions was found to be 290 kDa, possibly owing to the post-translational modification of the NG2 core protein, i.e., the shedding of its extracellular domain[33,50]. The reason for this discrepancy is unclear, these previous studies did show that the expression of the dominant NG2 core protein with a molecular weight of 300 kDa was higher in the ischemic core region, which is in agreement with our results

Summary

Introduction

Neuron-glia antigen 2 (NG2) glia are characterized by expression of surface chondroitin sulfate proteoglycan 41–5. The mycotoxin 3-NP selectively damages medium spiny neurons in the striatum via several mechanisms involving excitotoxicity and oxidative stress[37,38] This experimental model has advantages in the study of a series of pathophysiological responses, including changes in cellular dynamics and interactions among neuroglial cells in response to acute brain insults. This is because it leads to the formation of tissue lesions consisting of well-demarcated lesion cores where cell death occurs in neurons and in neuroglial cells, including astrocytes, microglia, and oligodendrocytes. The combined use of an immunoperoxidase method and a correlative approach using light and electron microscopy provided detailed and precise information regarding our ultrastructural observations in heterogeneous populations of NG2-expressing cells

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