CRE-mediated gene expression in cerebral ischemia

Although accumulating evidence indicates that cAMP response element binding protein (CREB) phosphorylation is upregulated after cerebral ischemia, it remains uncertain whether CREB phosphorylation induced after ischemia leads to CRE-mediated gene transcription and is involved in cell survival or not. Using CRE-LacZ transgenic mice, we demonstrated that CRE-mediated gene expression was found in a subset of pCREB-positive neurons after transient global and focal cerebral ischemia and in cultured neurons after exposure to glutamate. Treatment with CRE-decoy oligonucleotide suppressed upregulation of BCL-2 expression and accelerated neuronal damage after exposure to glutamate. CRE-mediated gene expression occurs in neurons after metabolic stresses and exerts its neuroprotective action through production of survival-promoting molecules such as anti-apoptotic protein BCL-2.