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Cyclic AMP response element (CRE) is a specific DNA sequence, which mediates transcriptional activation in the response to the cyclic AMP-activated and protein kinase A dependent signaling pathway. In the present study, phosphorylated CRE binding protein (CREB) immunoreactivity was mainly localized in the white matter of chick central nervous system (CNS). We have further confirmed the specificity of phospho-CREB immunoreaction in myelin using demyelinated optic nerve induced by lysophophatidylcholine (LPC), which is known to produce demyelination with little axonal damage. Double immunofluorescent analyses with myelin basic protein (MBP) and transferrin binding protein (TfBP), oligodendrocyte marker showed that phospho-CREB recognized a myelin-related protein in chick. Immunoblot analyses showed that phospho-CREB recognized a protein with molecular weights of approximately 70 kDa. Our data suggest that the antigen recognized by phospho-CREB is a myelin-associated protein in the chick CNS.