Activation of the transcription factor NF-kappaB after in vivo perforant path LTP in the mouse hippocampus. Hippocampus

RAMIRO FREUDENTHAL,; ARTURO GABRIEL ROMANO; ARYEH ROUTTENBERG,

HIPPOCAMPUS

Año: 2004 vol. 14 p. 677 - 683

1050-9631

There is increasing evidence that transcription factors (TFs) play a critical role in maintaining later phases of hippocampal long-term potentation (LTP). We have been led to study the role in synaptic plasticity of the powerful, yet generally unheralded, NF-kB TF because it may serve as both a signaling molecule after its activation at the synapse and then a transcription initiator upon reaching the nucleus.  Here we show that LTP activates NF-kB in the intact mouse hippocampus. Mice were sacrificed 15 min after 1 of 3 treatments: tetanization (high frequency stimulation, HFS), low frequency stimulation (LFS) or no stimulation (CT).  In a first study, nuclear NF-kB activity from hippocampus was estimated by electrophoretic mobility shift assays (EMSAs). A higher level of hippocampal TF binding to the NF-kB recognition element was found in the HFS group compared to LFS or CT.  In a second study, NF-kB activity was evaluated by immunohistochemistry with a specific antibody that recognizes the activated form of NF-kB.  This antibody binds to the exposed nuclear location sequence on the p65 subunit of NF-kB consequent to its dissociation from the inhibitory IkB molecule.  In the 4 subfields of hippocampus examined -granule cell layer, hilus of the dentate gyrus, CA3 and CA1 pyramidal fields of the hippocampal gyrus- the highest levels of activated NF-kB, statistically significant in all cases, were found after HFS.  In certain comparisons, LFS animals also showed significant elevation with respect to CT.  These results support the role of NF-kB as part of the synaptic signaling and transcriptional regulation mechanism required in long-term plasticity emphasizing the combinatorial nature of TF function.