A central challenge to modern neuroscience is to understand mechanisms of interneuronal communications, and the regulation and synthesis of endogenous sigal molecules in the brain, in both normal and pathological conditions. Unlike classical neurotransmitters and neuropeptides, gaseous nitric oxide (NO) is synthesized and released without the intermediary of special storage, subsequently freely crossing membrane barriers and affecting targets relatively large distances away, by direct covalent bonding. Although NO is crucial for most of the major neuronal functions (including learning, memory, differentiation and apoptosis), the resulting NO action depends on its local concentrations and the local microenvironment. NO can act either as a versatile signal molecule, and neuroprotective agent, or as a prominent neurotoxic intermediate. The development of postschemic brain injury, stroke, and neurodegenerative diseases are directly associated with a prominent overproduction of NO. NO synthase (NOS) is accepted as the only source of NO synthesis in the nervous system, and, although NOS inhibitors show promise as pharmacological instruments to prevent overproduction of NO, their effectiveness is controversial. However, since all these pathologies are generally associated with tissue acidification, we propose an alternative NOS-independent mechanism of NO formation in the nervous system, the non-enzymatic NO synthesis from nitrites in acidified and reducing micro-environments. This synthetic pathway may account for the excess O in these pathologies. Nitrites themselves are the main product of NO oxidation and can be accumulated in specific cells and tissues. Furthermore, due to the relatively high endogenous nitrite concentrations and the substantial pH transients associated with neuronal activity, this pathway is likely an additional mechanism for tonic NO production under normal conditions. The long-term objectives of this proposal are to analyze the distribution and functional significance of this complimentary NOS-independent pathway of NO formation in the nervous tissues, and, specifically, to characterize nitregic (NO producing) neuron and their postsynaptic targets. To separate enzymatic and non-enzymatic No synthesis we will use selective NOS inhibitors and microchemical analysis of major metabolites involved in these two pathways. Microelectrode electrical recording and pH1 measurements will provide further functional chracterization of individual nitregic neurons. Thus, significant gains can be made in our understanding of the synthesis of this gaseous messenger in the brain. This work will also contribute to our understanding of the neural functions in normal and pathological conditions.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-MDCN-5 (01))
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Nichols, Paul L
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University of Florida
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Striedter, Georg F; Belgard, T Grant; Chen, Chun-Chun et al. (2014) NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species. Brain Behav Evol 83:1-8
Striedter, Georg F; Belgard, T Grant; Chen, Chun-Chun et al. (2014) NSF workshop report: discovering general principles of nervous system organization by comparing brain maps across species. J Comp Neurol 522:1445-53
De Lisa, Emilia; De Maio, Anna; Moroz, Leonid L et al. (2012) Characterization of novel cytoplasmic PARP in the brain of Octopus vulgaris. Biol Bull 222:176-81
Moroz, L L (2012) Phylogenomics meets neuroscience: how many times might complex brains have evolved? Acta Biol Hung 63 Suppl 2:3-19
Kocot, Kevin M; Cannon, Johanna T; Todt, Christiane et al. (2011) Phylogenomics reveals deep molluscan relationships. Nature 477:452-6
Philippe, Hervé; Brinkmann, Henner; Copley, Richard R et al. (2011) Acoelomorph flatworms are deuterostomes related to Xenoturbella. Nature 470:255-8
Moroz, Leonid L (2011) Aplysia. Curr Biol 21:R60-1
Moroz, Leonid L; Kohn, Andrea B (2011) Parallel evolution of nitric oxide signaling: diversity of synthesis and memory pathways. Front Biosci (Landmark Ed) 16:2008-51
Choi, Sun-Lim; Lee, Yong-Seok; Rim, Young-Soo et al. (2010) Differential evolutionary rates of neuronal transcriptome in Aplysia kurodai and Aplysia californica as a tool for gene mining. J Neurogenet 24:75-82
Reyes-Colón, Dalynés; Vázquez-Acevedo, Nietzell; Rivera, Nilsa M et al. (2010) Cloning and distribution of a putative octopamine/tyramine receptor in the central nervous system of the freshwater prawn Macrobrachium rosenbergii. Brain Res 1348:42-54

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