Guyon A, Skrzydelski D, De Giry I, Rovère C, Conductier G, Trocello J M, Daugé V, Kitabgi P, Rostène W, Nahon J L, Mélik Parsadaniantz S
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UNSA, UMR, 6097 CNRS, 660 Route des Lucioles, Sophia Antipolis, 06560, Valbonne, France.
Neuroscience. 2009 Sep 15;162(4):1072-80. doi: 10.1016/j.neuroscience.2009.05.048. Epub 2009 May 27.
Accumulating evidence show that chemokines can modulate the activity of neurons through various mechanisms. Recently, we demonstrated that CCR2, the main receptor for the chemokine CCL2, is constitutively expressed in dopamine neurons in the rat substantia nigra. Here we show that unilateral intranigral injections of CCL2 (50 ng) in freely moving rats increase extracellular concentrations of dopamine and its metabolites and decrease dopamine content in the ipsilateral dorsal striatum. Furthermore, these CCL2 injections are responsible for an increase in locomotor activity resulting in contralateral circling behavior. Using patch-clamp recordings of dopaminergic neurons in slices of the rat substantia nigra, we observed that a prolonged exposure (>8 min) to 10 nM CCL2 significantly increases the membrane resistance of dopaminergic neurons by closure of background channels mainly selective to potassium ions. This leads to an enhancement of dopaminergic neuron discharge in pacemaker or burst mode necessary for dopamine release. We provide here the first evidence that application of CCL2 on dopaminergic neurons increases their excitability, dopamine release and related locomotor activity.
越来越多的证据表明，趋化因子可通过多种机制调节神经元的活性。最近，我们证明趋化因子CCL2的主要受体CCR2在大鼠黑质的多巴胺能神经元中组成性表达。在此我们表明，在自由活动的大鼠中单侧黑质内注射CCL2（50 ng）可增加细胞外多巴胺及其代谢产物的浓度，并降低同侧背侧纹状体中的多巴胺含量。此外，这些CCL2注射导致运动活性增加，从而导致对侧转圈行为。使用大鼠黑质切片中多巴胺能神经元的膜片钳记录，我们观察到长时间暴露（>8分钟）于10 nM CCL2会通过主要对钾离子具有选择性的背景通道关闭而显著增加多巴胺能神经元的膜电阻。这导致多巴胺释放所需的起搏器或爆发模式下多巴胺能神经元放电增强。我们在此提供首个证据，表明在多巴胺能神经元上应用CCL2可增加其兴奋性、多巴胺释放及相关的运动活性。
