Phosphodiesterase-7 inhibition increases oligodendroglial differentiation

Abstract

cAMP levels play an important role in the inflammatory response involved in many neurodegenerative disorders. The use of specific inhibitors for the different isoforms of phosphodiesterase family, particularly cAMP-specific PDE, have recently emerged as important drug target for the treatment of this kind of diseases. Our group have detected the expression of phosphodiesterase-7 (PDE7) in oligodendrocyte precursor cells (OPCs) isolated from P0 and P15 mice cerebral cortex. This cells are present in the mice Central Nervous System during development and during the adulthood and the may act as a source of new oligodendrocytes that replaces death oligodendrocytes. However, in demylinating disesases, such as Multiple Esclerosis, endogenous OPCs are not able to repair the injury or replace death oligodendrocytes. In vitro, we have demonstrated that two PDE7 selective inhibitors, TC 3.6 and VP 1.15, increase OPCs differentiation towards mature oligodendrocytes. This finding, combined with the already known anti-inflammatory effect carried out by these PDE7 inhibitors, identify them as a potential therapeutic agents for the treatment of Multiple Esclerosis. The knowledge of factors that affect the biology of OPCs results critical for the possible remyelination in this kind of pathologies. Funded: Ministerio Economía y Competitividad (SAF2009-07842), partially by F.E.D.E.R.; European Union, “Una manera de hacer Europa”, Gobierno de Castilla-La-Mancha (PI2009-26; PAI2010/012), Fundación Eugenio Rodríguez Pascual, Red Española de Esclerosis Múltiple (RETICS RD07/0060/2007, RD07/0060/0015). EM has a pre-doctoral fellowship from Ministerio Economía y Competitividad (SAF2009-07842).Peer Reviewe