The pattern of glutamate-induced nitric oxide dynamics in vivo and its correlation with nNOS expression in rat hippocampus, cerebral cortex and striatum.
Nitric oxide (NO) is a diffusible intercellular messenger, acting via volume signaling in the brain and, therefore, the knowledge of its temporal dynamics is determinant to the understanding of its neurobiological role. However, such an analysis in vivo is challenging and indirect or static approaches are mostly used to infer NO bioactivity. In the present work we measured the glutamate-dependent NO temporal dynamics in vivo in the hippocampus (CA1, CA3 and DG subregions), cerebral cortex and striatum, using NO selective microelectrodes. Concurrently, the immunolocalization of nNOS was evaluated in each region. A transitory increase in NO levels occurred at higher amplitudes in the striatum and hippocampus relatively to the cortex. In the hippocampus, subtle differences in the profiles of NO signals were observed along the trisynaptic loop, with CA1 exhibiting the largest signals. The topography of NO temporal dynamics did not fully overlap with the pattern of the density of nNOS expression, suggesting that, complementary to the distribution of nNOS, the local regulation of NO synthesis as well as the decay pathways critically determine the effective NO concentration sensed by a target within the diffusional spread of this free radical. In sum, the rate and pattern of NO changes here shown, by incorporating regulatory mechanisms and processes that affect NO synthesis and decay, provide refined information critical for the understanding of NO multiple actions in the brain.
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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Lourenço
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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Ferreira
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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Santos
Institute of Neurobiology, Slovak Academy of Sciences, Soltésovej 4, 040 01 Kosice, Slovak Republic.
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Lukacova
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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Barbosa
Faculty of Pharmacy and Center for Neurosciences and Cell Biology, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: laranjin@ci.uc.pt.
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Laranjinha
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism; D056654:CA3 Region, Hippocampal / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009569:Nitric Oxide; D018698:Glutamic Acid; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat
Cerebral cortex; Hippocampus; Microelectrode; Nitric oxide dynamics; Nitric oxide synthase; Striatum