Effect of cyclic AMP on the expression of myelin basic protein species andmyelin proteolipid protein in committed oligodendrocytes: Differential involvement of the transcription factor CREB

Our previous results support the idea that CREB (cyclic AMP-response elemen t binding protein) may be a mediator of neuroligand and growth factor signa ls that, coupled to different signal transduction pathways, play different roles at specific stages of oligodendrocyte development. In the early stage s, when cells are immature precursors, CREB may play a role as a mediator o f protein kinase C (PKC)/mitogen-activated protein kinase (MAPK) pathways r egulating cell proliferation. In contrast, at a later stage, when cells are already committed oligodendrocytes, CREB seems to play an important role a s a mediator in the stimulation of myelin basic protein (MBP) expression by cyclic AMP (cAMP). In this study, we have investigated whether cAMP and CR EB play a role in regulating the expression of all or on the other hand par ticular MBP isoforms. The results indicated that treatment of committed oli godendrocytes with the cAMP analogue db-cAMP results in a pattern of expres sion of MBP-related polypeptides that most closely resembles the pattern of MBPs observed in cerebra from adult animals. Experiments in which CREB exp ression was inhibited using a CREB antisense oligonucleotide, suggested tha t CREB is involved in the cAMP-dependent stimulation of all the MBP isoform s. In contrast, we have found that db-cAMP stimulates the expression of mye lin proteolipid protein (PLP) in a process that occurs despite inhibition o f CREB expression. These results support the idea that cAMP stimulates the maturation of oligodendrocytes and stress the fact multiple mechanisms may convey the action of this second messenger modulating oligodendrocyte diffe rentiation and myelination. (C) 2001 Wiley-Liss, Inc.