_-Tocopherol and _-tocopheryl phosphate interact with the cannabinoid system in the rodent hippocampus-

Authors
N. Crouzin, M.-C. de Jesus Ferreira, C. Cohen-Solal, C. m'kadmi, N. Bernad et al

Lab
UMR 5247–CNRS–Université Montpellier 1–Université Montpellier 2, Institut des Biomolécules Max Mousseron, Montpellier, France.

Journal
Free Radical Biology and Medicine

Abstract
_-Tocopherol (_-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 _-tocopherol in the brain are associated with neuronal dysfunctions ranging from mood disorders to neurodegeneration. All these behavioral effects of _-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 _-tocopherol and of its natural phosphate derivative, _-tocopheryl phosphate (_-TP), on synaptic transmission in rodent hippocampus. These compounds had opposite actions on both glutamatergic and GABAergic transmission: whereas _-TOH potentiated these transmissions, _-TP inhibited them. Interestingly, these effects were both mediated by cannabinoid receptors (CB1Rs), because they were blocked by the CB1R antagonist AM251. Although _-tocopherol and _-tocopheryl phosphate did not directly bind CB1R, both _-TP and CB1R agonists inhibited forskolin-evoked Erk1/2 phosphorylation in a nonadditive manner. Furthermore, both _-tocopherol and _-tocopheryl phosphate attenuated depolarization-induced suppression of excitation and CB1R agonist-mediated hypothermia. Therefore, we identify _-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.