title: α-tocopherol and α-tocopheryl phosphate interact with the cannabinoid system in the rodent hippocampus.
abstract: 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.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247–CNRS–Université Montpellier 1–Université Montpellier 2, 34095 Montpellier Cedex 5, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Crouzin
authors.forename: Marie-Céleste
authors.initials: MC
authors.lastname: de Jesus Ferreira
authors.forename: Catherine
authors.initials: C
authors.lastname: Cohen-Solal
authors.forename: Céline
authors.initials: C
authors.lastname: M'Kadmi
authors.forename: Nicole
authors.initials: N
authors.lastname: Bernad
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.forename: Gérard
authors.initials: G
authors.lastname: Barbanel
authors.forename: Michel
authors.initials: M
authors.lastname: Vignes
authors.forename: Janique
authors.initials: J
authors.lastname: Guiramand
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D043882:Receptors, Cannabinoid / Q000378:metabolism; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D063386:Cannabinoid Receptor Agonists; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; C012552:alpha-tocopherol phosphate; D024502:alpha-Tocopherol