title: Methylphenidate Increases Glutamate Uptake in Bergmann Glial Cells.
abstract: Glutamate, the main excitatory transmitter in the vertebrate brain, exerts its actions through the activation of specific membrane receptors present in neurons and glial cells. Over-stimulation of glutamate receptors results in neuronal death, phenomena known as excitotoxicity. A family of glutamate uptake systems, mainly expressed in glial cells, removes the amino acid from the synaptic cleft preventing an excessive glutamatergic stimulation and thus neuronal damage. Autism spectrum disorders comprise a group of syndromes characterized by impaired social interactions and anxiety. One or the most common drugs prescribed to treat these disorders is Methylphenidate, known to increase dopamine extracellular levels, although it is not clear if its sedative effects are related to a plausible regulation of the glutamatergic tone via the regulation of the glial glutamate uptake systems. To gain insight into this possibility, we used the well-established model system of cultured chick cerebellum Bergmann glia cells. A time and dose-dependent increase in the activity and protein levels of glutamate transporters was detected upon Methylphenidate exposure. Interestingly, this increase is the result of an augmentation of both the synthesis as well as the insertion of these protein complexes in the plasma membrane. These results favour the notion that glial cells are Methylphenidate targets, and that by these means could regulate dopamine turnover.
authors.affiliation: Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000, Mexico, DF, Mexico.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Guillem
authors.affiliation: Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000, Mexico, DF, Mexico.
authors.forename: Zila
authors.initials: Z
authors.lastname: Martínez-Lozada
authors.affiliation: Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000, Mexico, DF, Mexico.
authors.forename: Luisa C
authors.initials: LC
authors.lastname: Hernández-Kelly
authors.affiliation: Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000, Mexico, DF, Mexico.
authors.forename: Esther
authors.initials: E
authors.lastname: López-Bayghen
authors.affiliation: Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000, Mexico, DF, Mexico.
authors.forename: Bruno
authors.initials: B
authors.lastname: López-Bayghen
authors.affiliation: Clínica Neurocom, 03100, Mexico, DF, Mexico.
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Calleros
authors.affiliation: Clínica Neurocom, 03100, Mexico, DF, Mexico.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Campuzano
authors.affiliation: Laboratorio de Neurotoxicología, Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado Postal 14-740, 07000, Mexico, DF, Mexico. arortega@cinvestav.mx.
authors.forename: Arturo
authors.initials: A
authors.lastname: Ortega
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002642:Chick Embryo; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008774:Methylphenidate / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018765:Dopamine Uptake Inhibitors; D027341:Excitatory Amino Acid Transporter 1; D008774:Methylphenidate; D001224:Aspartic Acid; D018698:Glutamic Acid; D012313:RNA; D004298:Dopamine
keywords: Bergmann glia; Excitatory amino acid transporters; Methylphenidate; Translational control