STABILIZATION OF DENDRITIC MESSENGER-RNAS BY NITRIC-OXIDE ALLOWS LOCALIZED, ACTIVITY-DEPENDENT ENHANCEMENT OF HIPPOCAMPAL PROTEIN-SYNTHESIS

A small number of mRNA species are not restricted to the neuronal cell body, but are also present in neuronal dendrites, The levels of two o f these dendritic mRNAs, encoding the microtubule-associated protein M AP2 and the oc subunit of calcium/calmodulin-dependent protein kinase II (CamKII alpha), are increased rapidly by high-frequency synaptic ac tivity or by release of nitric oxide. To test the hypothesis that post -transcriptional mechanisms might contribute to this modulation, prima ry cultures of rat hippocampal neurons were exposed to s-nitroso-N-ace tyl penicillamine (SNAP, 200 mu M) or vehicle, and mRNA stability was determined. The stability of both CamKII alpha mRNA and MAP2 mRNA was increased by SNAP treatment, whereas the stabilities of tubulin T26 mR NA and proenkephalin mRNA were unaffected. When the intensity of stain ing for MAP2 immunoreactivity and CamKII alpha immunoreactivity was mo nitored in cultured hippocampal neurons, nitric oxide-releasing agents induced increases in staining intensity that were dependent on protei n synthesis but not on mRNA synthesis. These results show that nitric oxide can selectively stabilize CamKII alpha mRNA and MAP2 mRNA, leadi ng to increased synthesis of the corresponding proteins. This demonstr ates a mechanism whereby the presence of a particular mRNA in the vici nity of a synapse permits the levels of the protein product to be regu lated by synaptic activity in a manner that is both prolonged and also highly localized to the region of stimulation. Thus, the dependence o f sustained synaptic plasticity on de novo protein synthesis need not entail a loss of anatomical specificity.