CCAAT/enhancer binding protein β deficiency provides cerebral protection following excitotoxic injury

Abstract

The CCAAT/enhancer-binding protein β (C/EBPβ, also known as CEBPB) was first identified as a regulator of differentiation and inflammatory processes in adipose tissue and liver. Although C/EBPβ was initially implicated in synaptic plasticity, its function in the brain remains largely unknown. We have previously shown that C/EBPβ regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have demonstrated that the expression of C/EBPβ is notably increased in the hippocampus in a murine model of excitotoxicity. Mice lacking C/EBPβ showed a reduced inflammatory response after kainic acid injection, and exhibited a dramatic reduction in pyramidal cell loss in the CA1 and CA3 subfields of the hippocampus. These data reveal an essential function for C/EBPβ in the pathways leading to excitotoxicity-mediated damage and suggest that inhibitors of this transcription factor should be evaluated as possible neuroprotective therapeutic agents.