Reactive astrocytes express estrogen receptors in the injured primate brain

Previous studies have suggested that estrogen may regulate the expression of genes related to the inflammatory response within the nervous system, particularly within glia. In the present study, we examined whether injury induces estrogen sensitivity in reactive glia in the primate brain. Three adult Macaca fascicularis (cynomolgous) monkeys received unilateral fimbria fornix transections followed by chronic intracranial cannula implants through which a vehicle solution was infused intracerebroventricularly for a 4-week period. Astrocytes adjacent to areas of parenchymal disruption caused either by the lesion or by the instrumentation procedure became reactive, as evidenced by cellular hypertrophy and up-regulation of glial fibrillary acidic protein (GFAP) immunolabeling. Of note, specific estrogen receptor-alpha immunolabeling also was induced adjacent to injured regions, and this labeling strictly colocalized with GFAP immunoreactivity upon double fluorescent confocal immunolabeling. Induction of estrogen receptor immunoreactivity in reactive astrocytes occurred in all monkeys examined, whereas nonreactive glia distant from disrupted regions did not exhibit estrogen receptor labeling. Thus, expression of estrogen receptors is up-regulated in reactive astrocytes of the primate brain, potentially allowing estrogen to modulate aspects of the central nervous system's inflammatory response to injury.