title: Coupling of ascorbate and nitric oxide dynamics in vivo in the rat hippocampus upon glutamatergic neuronal stimulation: a novel functional interplay.
abstract: BACKGROUND
  Ascorbate and neuronal-derived nitric oxide (NO) play regulatory roles in the brain that tare dependent on their compartmentalization and diffusion. Glutamatergic activation triggers both ascorbate fluxes toward extracellular medium and NO production. The information on the profiles of change in time and space upon glutamatergic activation is scarce and yet this knowledge is important for the understanding of ascorbate and NO functions in vivo, in particular in the case of a coupled interaction between both dynamics.
  
  
  OBJECTIVE
  NO produced upon NMDA receptor activation is a modulator of ascorbate release to the extracellular space.
  
  
  METHODS
  In this work, carbon fiber microelectrodes for simultaneous measurements of these substances in the hippocampus were used to collect information about ascorbate and NO dynamic profiles in real time.
  
  
  RESULTS
  Glutamate stimulation evoked transient ascorbate and NO signals with high degree of spatial and temporal correlation between them. Combined experiments encompassing direct stimulus with NO and inhibitors of glutamate uptake and nNOS provided additional evidence supporting the modulator role of NO in the release of ascorbate to the extracellular space.
  
  
  CONCLUSIONS
  The coupling between NO and ascorbate upon glutamatergic activation points to a functional impact on the activities of both compounds and, although the precise molecular mechanism needs to be clarified, such a coupling lays the foundations for new regulatory mechanisms in the brain.
authors.affiliation: Center for Neuroscience, Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal.
authors.forename: Nuno R
authors.initials: NR
authors.lastname: Ferreira
authors.affiliation: Center for Neuroscience, Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal.
authors.forename: C F
authors.initials: CF
authors.lastname: Lourenço
authors.affiliation: Center for Neuroscience, Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000 548 Coimbra, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.affiliation: Center for Neuroscience, Cell Biology, University of Coimbra, 3004 517 Coimbra, Portugal; Faculty of Pharmacy, University of Coimbra, 3000 548 Coimbra, Portugal. Electronic address: laranjin@ci.uc.pt.
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000818:Animals; D001204:Ascorbate Oxidase / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism*; D002244:Carbon; D000077482:Carbon Fiber; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D016202:N-Methylaspartate / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
chemical_list: D000077482:Carbon Fiber; D004791:Enzyme Inhibitors; D007191:Indazoles; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D016202:N-Methylaspartate; D002244:Carbon; D001204:Ascorbate Oxidase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D001205:Ascorbic Acid; C080122:7-nitroindazole
keywords: Brain ascorbate; Brain nitric oxide; Glutamate; Microelectrodes; Real time in vivo dynamics