Inhibition of phosphodiesterase-4 promotes oligodendrocyte precursor cell differentiation and enhances CNS remyelination

ABSTRACT: We used transcription-profiling to identify mitogen-activated protein kinase (Mapk) signaling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signaling by elevation of intracellular levels of cAMP using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolyzing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination. Study was conducted to identify the genes that are differentialy regulated during early time point of OPC differentiation.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Szymon Myrta 

PROVIDER: E-GEOD-50042 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress