Dynamic and interacting profiles of *NO and O2 in rat hippocampal slices

Center for Neurosciences and Cell Biology, University of Coimbra, 3000 Coimbra, Portugal.
Free Radical Biology and Medicine (Impact Factor: 5.74). 04/2010; 48(8):1044-50. DOI: 10.1016/j.freeradbiomed.2010.01.024
Source: PubMed


Nitric oxide (*NO) is a ubiquitous signaling molecule that participates in the neuromolecular phenomena associated with memory formation. In the hippocampus, neuronal *NO production is coupled to the activation of the NMDA-type of glutamate receptor. Although *NO-mediated signaling has been associated with soluble guanylate cyclase activation, cytochrome oxidase is also a target for this gaseous free radical, for which *NO competes with O(2). Here we show, for the first time in a model preserving tissue cytoarchitecture (rat hippocampal slices) and at a physiological O(2) concentration, that endogenous NMDA-evoked *NO production inhibits tissue O(2) consumption for submicromolar concentrations. The simultaneous real-time recordings reveal a direct correlation between the profiles of *NO and O(2) in the CA1 subregion of the hippocampal slice. These results, obtained in a system close to in vivo models, strongly support the current paradigm for O(2) and *NO interplay in the regulation of cellular respiration.

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Available from: Rui M Barbosa
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    • "The NO-inhibited respiration lowers the steepness of intracellular O 2 gradients and allows O 2 to diffuse further along its gradient, extending the space of adequate tissue oxygenation away from the blood vessel. Endogenous NO production has been shown to inhibits tissue O 2 consumption in hippocampal slices at physiological O 2 concentration, strongly supporting the current paradigm for O 2 and NO interplay in the regulation of cellular respiration (Ledo et al., 2010). "
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    • "By using this methodological approach we were able to show that NMDA-evoked •NO concentration dynamics is heterogeneous along the trisynaptic loop in the rat hippocampus [57]. We also provided evidence that the AMPAr in addition to the NMDAr could contribute to the fine tuning of glutamate-dependent •NO production [58] and that NMDA-evoked •NO production inhibits tissue O2 consumption for submicromolar concentrations [59]. "
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    • "While more data is needed to better address this question, perfusing slices with a 20% O2 solution might be closer to physiological conditions and is unlikely to induce cell death (D'Agostino et al., 2007). In a recent study, Ledo et al. (2010) simultaneously measured NO and O2 levels 200 μm deep into the slice using an aCSF solution bubbled with 95% O2–5% CO2; under these conditions O2 levels were around 57.3 ± 38.2 μM. To our knowledge the outcome of 20% O2 levels on NO availability at different depths of the brain slice has not been explored and would need further consideration, given the steep O2 gradient from the surface of the slice to deeper layers (∼200 μm) (Ledo et al., 2005). "
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