Research report
Gene expression of the transcription factor NF-κ B in hippocampus: regulation by synaptic activity

https://doi.org/10.1016/0169-328X(95)00229-LGet rights and content

Abstract

NF-κ B is a potent transcriptional activator that resides in latent form in the cytoplasm complexed to its inhibitor I κ B. Phosphorylation of I κ B by protein kinase C (PKC) releases NF-κ B, enabling its translocation to the nucleus. Since PKC can activate NF-κ B and PKC is activated by long-term potentiation (LTP), we investigated NF-κ B expression after hippocampal LTP induced in vivo. We first described the expression of the NF-κ B subunits, p50 and p65, and I κ B α mRNAs, in each cell field of the hippocampus. In other brain locations I κ B α mRNA exhibited a more selective expression than p50 and p65. We then demonstrated specific NF-κ B-like DNA-binding activity in hippocampal whole-cell extracts and in synaptosomes using electrophoretic mobility shift assays by the following criteria: (1) latent binding was revealed after deoxycholate treatment; (2) binding was competed off by unlabeled κ B oligonucleotides; and (3) antibodies to either p50 or p65 blocked binding. Since p50 gene expression is auto-regulated by NF-κ B, we used its expression as a reporter for NF-κ B activity using quantitative in situ hybridization. Both p50 and p65 increased their expression in response to either LTP-inducing or low-frequency control stimulation, although the increase in p65 mRNA levels was greater after LTP than control stimulation. In contrast to p50 and p65, I κ B α hybridization levels were not increased, but were inversely correlated with the magnitude of LTP. Since NF-κ B subunit gene expression in the hippocampus is increased by augmented synaptic activity, NF-κ B activation may contribute to alterations in target gene expression that accompany activity-dependent synaptic plasticity, but only in a combinatorial fashion with other transcription factors.

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    Present address: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.

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