Dipartimento di Medicina dei Sistemi, Università Tor Vergata, Via Montpellier 1, 00133 Rome, Italy; Fondazione Santa Lucia/Centro Europeo per la Ricerca sul Cervello (CERC), Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Neuroscience. 2013 Oct 10;250:232-9. doi: 10.1016/j.neuroscience.2013.06.069. Epub 2013 Jul 12.
Proinflammatory cytokines such as tumor necrosis factor-α and interleukin-1β (IL1β) regulate both excitatory and inhibitory synaptic transmission in the central nervous system. The interaction between IL1β and endocannabinoid system (ECS) is also emerging, based on the evidence that IL1β effects on striatal spontaneous excitatory and inhibitory postsynaptic currents are regulated by transient receptor potential vanilloid 1 (TRPV1) channels, members of the ECS. Furthermore, IL1β has also been shown to control the sensitivity of cannabinoid CB1 receptors controlling GABA transmission (CB1Rs(GABA)) in the striatum. To better detail the synaptic action of IL1β, and to clarify its complex interaction with the ECS, here we investigated the possible interplay between IL1β and CB1Rs controlling glutamate transmission (CB1Rs(glu)), other critical elements of the ECS. Our results show that the sensitivity of CB1Rs(glu) is fully blocked in the presence of IL1β in corticostriatal brain slices, and that the protein kinase C/TRPV1 pathway is involved in this effect. IL1β failed to modulate the sensitivity of glutamate synapses to the stimulation of GABAB receptors. We also provided evidence that IL1β-CB1Rs(GABA) but not IL1β-CB1Rs(glu) interaction is under the control of the brain-derived neurotrophic factor (BDNF)/trkB signaling and of lipid raft composition, because BDNF gene partial deletion, pharmacological blockade of trkB and membrane cholesterol removal with methyl-β-cyclodextrin all blocked IL1β-mediated inhibition of CB1Rs(GABA) but left unaltered the sensitivity of CB1Rs(glu) to this cytokine. Our results provide further evidence that synaptic transmission and the ECS are regulated by IL1β in the striatum.
促炎细胞因子，如肿瘤坏死因子-α和白细胞介素-1β（IL1β），调节中枢神经系统中兴奋性和抑制性突触传递。IL1β 与内源性大麻素系统（ECS）之间的相互作用也正在出现，因为有证据表明，IL1β 对纹状体自发性兴奋性和抑制性突触后电流的作用受到瞬时受体电位香草素 1（TRPV1）通道的调节，TRPV1 通道是 ECS 的成员。此外，IL1β 还被证明可以控制控制 GABA 传递的大麻素 CB1 受体（CB1Rs（GABA））在纹状体中的敏感性。为了更详细地描述 IL1β 的突触作用，并阐明其与 ECS 的复杂相互作用，我们在这里研究了 IL1β 与控制谷氨酸传递的 CB1 受体（CB1Rs（glu））之间可能的相互作用，ECS 的其他关键元素。我们的结果表明，在皮质纹状体脑片中存在 IL1β 的情况下，CB1Rs（glu）的敏感性被完全阻断，而蛋白激酶 C/TRPV1 途径参与了这种作用。IL1β 不能调节谷氨酸突触对 GABAB 受体刺激的敏感性。我们还提供了证据表明，IL1β-CB1Rs（GABA）而不是 IL1β-CB1Rs（glu）相互作用受脑源性神经营养因子（BDNF）/trkB 信号和脂筏组成的控制，因为 BDNF 基因部分缺失、trkB 的药理学阻断和用甲基-β-环糊精去除膜胆固醇都阻断了 IL1β 介导的 CB1Rs（GABA）抑制，但对 CB1Rs（glu）对这种细胞因子的敏感性没有改变。我们的结果进一步证明，在纹状体中，突触传递和 ECS 受 IL1β 调节。
