Coupling of ascorbate and nitric oxide dynamics in vivo in the rat hippocampus upon glutamatergic neuronal stimulation: a novel functional interplay.

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. NO produced upon NMDA receptor activation is a modulator of ascorbate release to the extracellular space. 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. 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. 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.