Transient expression of the NG2 proteoglycan by a subpopulation of activated macrophages in an excitotoxic hippocampal lesion.

Abstract

Cells that express the NG2 proteoglycan (NG2+ cells) constitute a large glial population in the normal mature rodent brain. They can differentiate into oligodendrocytes but are distinct from mature oligodendrocytes, astrocytes, microglia, and neurons. Changes in NG2+ cells were examined in kainic acid-induced excitotoxic lesions of the hippocampus, and the relationship between NG2+ cells and reactive astrocytes and microglia was investigated between 1 and 90 days after lesioning. Two types of reactive NG2+ cells with altered morphology and increased NG2 immunoreactivity were observed in the lesion. Early changes, consisting of an increase in NG2 immunoreactivity and the number of processes, were apparent 24 h after lesioning and persisted through 3 months. These cells were distinct from reactive astrocytes or activated microglia/macrophages. A second type of reactive NG2+ cells appeared 2 weeks after injection, following an influx of macrophages. They had large, round cell bodies with short processes and expressed the microglia/macrophage antigens OX42 and ED1. Single cells coexpressing NG2 and macrophage/microglial antigens could be isolated from the lesion. The number of NG2+/OX42+ cells gradually declined and disappeared by 3 months after injection. They did not express glial fibrillary acidic protein or the alpha receptor for platelet-derived growth factor, indicating that they are distinct from astrocytes or oligodendrocyte progenitor cells. Cells that coexpressed NG2 and OX42 were never observed in hippocampal slice cultures treated with kainic acid, suggesting that NG2+/OX42+ cells are not derived from endogenous resident brain cells. These findings demonstrate that NG2 expression is transiently upregulated on activated macrophages/microglia that appear during the chronic stage in an excitotoxic lesion in the adult CNS.