Phosphodiesterase 7 Inhibition Induces Dopaminergic Neurogenesis in Hemiparkinsonian Rats

Abstract

©AlphaMed Press 2015 Parkinson’s disease is characterized by a loss of dopaminergic neurons in a specific brain region, the ventralmidbrain.Parkinson’sdiseaseisdiagnosedwhenapproximately50%ofthedopaminergicneu-rons of the substantia nigra pars compacta (SNpc) have degenerated and the others are already af-fectedby the disease. Thus, itis conceivable that all therapeutic strategies, aimed at neuroprotection, start too late. Therefore, an urgent medical need exists to discover new pharmacological targets and noveldrugs withdisease-modifying properties.Inthisregard,modulationofendogenousadultneuro-genesis towardadopaminergic phenotypemightprovideanewstrategytotarget Parkinson’s disease by partially ameliorating the dopaminergic cell loss that occurs in this disorder. We have previously shown that a phosphodiesterase 7 (PDE7) inhibitor, S14, exerts potent neuroprotective and anti-inflammatory effectsin different rodent models ofParkinson’sdisease, indicating that this compound could represent a novel therapeutic agent to stop the dopaminergic cell loss that occurs during the progression of the disease. In this report we show that, in addition to its neuroprotective effect, the PDE7 inhibitor S14 is also able to induce endogenous neuroregenerative processes toward a dopami-nergic phenotype. We describe a population of actively dividing cells that give rise to new neurons in theSNpcofhemiparkinsonianratsaftertreatmentwithS14.Inconclusion,ourdataidentifyS14asanovel regulator of dopaminergic neuron generation.