CCAAT/enhancer binding protein beta deficiency provides cerebral protection following excitotoxic injury.
The CCAAT/enhancer-binding protein beta (C/EBPbeta, also known as CEBPB) was first identified as a regulator of differentiation and inflammatory processes in adipose tissue and liver. Although C/EBPbeta was initially implicated in synaptic plasticity, its function in the brain remains largely unknown. We have previously shown that C/EBPbeta regulates the expression of genes involved in inflammatory processes and brain injury. Here, we have demonstrated that the expression of C/EBPbeta is notably increased in the hippocampus in a murine model of excitotoxicity. Mice lacking C/EBPbeta 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/EBPbeta in the pathways leading to excitotoxicity-mediated damage and suggest that inhibitors of this transcription factor should be evaluated as possible neuroprotective therapeutic agents.
Cortes-Canteli
Marta
M
Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier, 4, Madrid, Spain.
Luna-Medina
Rosario
R
Sanz-Sancristobal
Marina
M
Alvarez-Barrientos
Alberto
A
Santos
Angel
A
Perez-Castillo
Ana
A
D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000517:prevention & control*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics*; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D051379:Mice; D051381:Rats
D022782:CCAAT-Enhancer-Binding Protein-beta; D007608:Kainic Acid