Les chimiokines, de nouveaux acteurs dans le système dopaminergique

Abstract

Previous neuroanatomical studies realized in our team allowed us to demonstrate the neuronal and glial expression of various chemokines and their receptors in central dopaminergic (DA) pathways. In the light of these original observations, we questioned the role of chemokines on the physiology of DA neuron and on the neurodegenerative process in the DA nigro-striatal pathway, which characterizes Parkinson's disease. We focused our attention on two particular chemokines, the Stromal cell-Derived Factor-1 (SDF-1/CXCL12) and the Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) and their cognate receptors CXCR4 and CCR2, as they are expressed constitutively in nearly all DA mesencephalic neurons. We demonstrated, by using in vivo and in vitro approaches, that SDF-1 and MCP-1 can modulate DA neurotransmission in the nigro-striatal pathway, modifying the electrophysiological state of the neuron and DA release, through their cognate receptors. These effects are produced through N-type high voltage-activated calcium currents for SDF-1 and potassium channels for MCP-1. We then discuss the possible implication of SDF-1 and its derivative SDF-1(5-67) in DA neurodegeneration.