Reactive astrocytes of the quinolinic acid-lesioned rat striatum express GFRalpha1 as well as GDNF in vivo

Abstract

Mechanical injury of the rodent striatum has recently been shown to cause a local increase in expression of mRNAs for glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor in the inflammatory cells, i.e., macrophages and activated microglia, respectively (3). An earlier study demonstrated an increase in GDNF mRNA levels in the adult rat striatum after administration of subseizure doses of N-methyl-d,l-aspartate and kainic acid (20) and identified astrocytes as the likely source of GDNF mRNA in the injected striatum. Our own recent work suggests that quinolinic acid (QA) induces moderate immunoreactivity to GDNF in a population of cells resembling reactive astrocytes within 1 week following intrastriatal injection (9). Therefore, the present follow-up experiment was performed with the aims: (I) to look at GDNF expression in the QA-injected striatum at 28 days, (II) to look for possible immunohistochemical expression of GFRalpha1 in the QA-injected striatum at the same observation time, and (III) to use confocal microscopy of double-immunofluorescence labeling of glial-cell-specific markers to identify the cell types expressing GDNF and GFRalpha1 in the striatum at 28 days following a QA injection. Our data indicate that GDNF immunoreactivity is high in the QA-injected striatum at 28 days and that the vast majority of cells displaying high labeling for GDNF also express glial fibrillary acidic protein and have a phenotype of reactive astrocytes. Interestingly, the same cells that express GDNF also display strong cytoplasmic immunolabeling to GFRalpha1.