Institut des Biomolécules Max Mousseron, UMR 5247–CNRS–Université Montpellier 1–Université Montpellier 2, 34095 Montpellier Cedex 5, France.
Free Radic Biol Med. 2011 Nov 1;51(9):1643-55. doi: 10.1016/j.freeradbiomed.2011.07.012. Epub 2011 Aug 4.
α-Tocopherol (α-TOH), a dietary component of vitamin E, is well known for its antioxidant capacity. Nevertheless, recent studies have pointed out non-anti-radical properties including cellular and genomic actions. Decreased levels of α-tocopherol in the brain are associated with neuronal dysfunctions ranging from mood disorders to neurodegeneration. All these behavioral effects of α-tocopherol deficiency probably do not rely simply on its anti-radical properties, but could also be reminiscent of a not-yet characterized neuromodulatory action. We have thus measured the direct actions of α-tocopherol and of its natural phosphate derivative, α-tocopheryl phosphate (α-TP), on synaptic transmission in rodent hippocampus. These compounds had opposite actions on both glutamatergic and GABAergic transmission: whereas α-TOH potentiated these transmissions, α-TP inhibited them. Interestingly, these effects were both mediated by cannabinoid receptors (CB1Rs), because they were blocked by the CB1R antagonist AM251. Although α-tocopherol and α-tocopheryl phosphate did not directly bind CB1R, both α-TP and CB1R agonists inhibited forskolin-evoked Erk1/2 phosphorylation in a nonadditive manner. Furthermore, both α-tocopherol and α-tocopheryl phosphate attenuated depolarization-induced suppression of excitation and CB1R agonist-mediated hypothermia. Therefore, we identify α-tocopherol as new lipid modulator of the cannabinoid system in the rodent hippocampus, i.e., a novel "non-anti-radical" action of vitamin E, which may have some preeminent impact in neuronal disorders associated with vitamin E deficiency.
α-生育酚（α-TOH）是维生素 E 的一种膳食成分，以其抗氧化能力而闻名。然而，最近的研究指出了其非自由基性质，包括细胞和基因组作用。大脑中 α-生育酚水平降低与从情绪障碍到神经退行性变的神经元功能障碍有关。α-生育酚缺乏的所有这些行为效应可能不仅仅依赖于其抗氧化特性，而且可能还类似于尚未确定的神经调节作用。因此，我们测量了 α-生育酚及其天然磷酸酯衍生物α-生育酚磷酸酯（α-TP）对啮齿动物海马体突触传递的直接作用。这些化合物对谷氨酸能和 GABA 能传递具有相反的作用：α-TOH 增强了这些传递，而α-TP 抑制了它们。有趣的是，这些作用均由大麻素受体（CB1R）介导，因为它们被 CB1R 拮抗剂 AM251 阻断。尽管 α-生育酚和α-生育酚磷酸酯本身不直接结合 CB1R，但α-TP 和 CB1R 激动剂均以非加性方式抑制forskolin 诱导的 Erk1/2 磷酸化。此外，α-生育酚和α-生育酚磷酸酯均可减轻去极化诱导的抑制兴奋和 CB1R 激动剂介导的体温降低。因此，我们将α-生育酚鉴定为啮齿动物海马体中大麻素系统的新型脂质调节剂，即维生素 E 的新“非抗氧化”作用，它可能对与维生素 E 缺乏有关的神经元疾病产生一些突出的影响。
