Glutamate-dependent activation of NF-κB during mouse cerebellum development

Abstract

NF-≃B and activator protein 1 (AP-1) are dimeric transcription factors involved in transcriptional regulation in many cells, including neurons. We have examined their activity during mouse cerebellum development, a postnatal process starting just after birth and completed by the fourth postnatal (PN) week. The activity of these factors was analyzed by binding of nuclear extracts to a synthetic oligonucleotide representing the ≃B site of human immunodeficiency virus or the AP-1 site of the urokinase promoter. NF-≃B activity was observed from 7 PN, was restricted to the developing cerebellum, and was not observed in the early postnatal neocortex and hippocampus. On the other hand, AP-1 activity was not found in cerebellum but was present in both neocortex and hippocampus. Moreover, a ≃B-driven transgene was found to be increasingly expressed in the cerebellum from 5 PN to 10 PN but not in the adult. The regulation of NF-≃B activation in mouse cerebellum was analyzed by intraperitoneal injection of glutamate receptor antagonists to 9 PN, mice, which abolished NF-≃B-binding activity, suggesting an endogenous loop of glutamate receptor activation. Glutamate receptor agonists, on the other hand, induced NF-≃B nuclear translocation in the cerebellum of 5 PN mice, which is a stage in which NF-≃B is not yet endogenously activated. This effect was specific for NF-≃B and not observed for AP-1. In adult mice, NF- ≃B activity was absent in the cerebellum and was not induced by intraperitoneal injection of glutamate receptor agonists. These data show that NF-≃B is specifically activated during cerebellum development and indicate an important role of glutamate receptors in this process.