The reciprocal relationship between NF-κB and CREB transcription sensitizes neurons to excitotoxicity (Zou and Crews 2006). This reciprocal relationship appears to result from the actions of kinases, such as protein kinase A, which activate CREB transcription but inhibit NF-κB activation. However, the reciprocal relationship also may represent differences between neuronal and glial signaling pathways, because regulation of CREB transcription principally occurs in neurons whereas NF-κB activation of pro-inflammatory genes primarily occurs in microglia.
