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Volume 17, Number 16, Issue of August 15, 1997 pp. 6057-6063
Copyright ©1997 Society for Neuroscience

Glutamate-Dependent Activation of NF-B During Mouse Cerebellum Development

Received March 24, 1997; revised May 16, 1997; accepted May 30, 1997.

Luisa Guerrini¹, Angela Molteni¹, Thomas Wirth³, Barbara Kistler³, and Francesco Blasi^{1, 2}

¹ Department of Genetics and Microbial Biology, University of Milan, 20133 Milan, Italy, ² Dipartimento di Biologia e Biotecnologia, San Raffaele Scientific Institute, 20100 Milan, Italy, and ³ Institute fuer Medinische Strahlenkunde und Zellforschung, 97078 Wurzburg, Germany

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.

Key words: NF-B; cerebellum; development; HIV; glutamate; transcription

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