Regulation of neuronal cell adhesion molecule expression by NF-kappa B

The neuronal cell adhesion molecule (NCAM) is a key mediator of structural plasticity in the central nervous system, but the mechanisms that control its expression are unknown. Equally, although the transcription factor NF-kappaB is present in the brain, few NF-kappaB-regulated genes relevant for central nervous system function have been identified. We have previously demonstrated that NF-kappaB is activated in neuronal cultures treated with kainic acid or nitric oxide. We show here that kainic acid or nitric oxide also increase the levels of NCAM mRNA and protein in neurons and that this induction of NCAM expression is sensitive to dexamethasone and to antisense, but not missense, oligonucleotides designed to suppress NF-kappaB synthesis. Nitric oxide also stimulates protein binding to an NF-kappaB site in the promoter of the NCAM gene. This indicates that NF-kappaB, which has recently been implicated in synaptic plasticity and also in the etiology of neurodegenerative disease, plays a crucial role in the activity-dependent regulation of NCAM gene expression. In addition, since both NCAM and NF-kappaB are present in the post-synaptic density, this represents a route allowing direct communication between the synapse and the nucleus.