The PPAR?/? Agonist GW0742 Induces Early Neuronal Maturation of Cortical Post-Mitotic Neurons: Role of PPAR?/? in Neuronal Maturation

Increasing evidences support that signalling lipids participate in synaptic plasticity and cell survival, and that the lipid signalling is closely associated with neuronal differentiation, learning and memory and with pathologic events such as epilepsy and Alzheimer's disease. The Peroxisome Proliferator-Activated Receptors (PPAR) are strongly involved in the fatty acid cell signalling, as many of the natural lypophylic compounds are PPAR ligands. We have previously shown that PPAR?/? is the main isotype present in cortical neuron primary cultures and that during neuronal maturation, PPAR?/? is gradually increased and activated. To get more insight into the molecular mechanism by which PPAR?/? may be involved in neuronal maturation processes, in this work a specific PPAR?/? agonist, GW0742 was used administered alone or in association with a specific PPAR?/? antagonist, the GSK0660 and the parameters involved in neuronal differentiation and maturation were assayed. The data obtained demonstrated the strong involvement of PPAR?/? in neuronal maturation, triggering the agonist an anticipation of neuronal differentiation and the antagonist abolishing the observed effects. These effects appear to be mediated by the activation of both BDNF canonical (BDNF7TrkB) pathway. This article is protected by copyright. All rights reserved.