Increased neurons containing neuronal nitric oxide synthase in the brain of a hypoxic-ischemic neonatal rat model

Objective: To conduct a comparative study of the structural organization of internuclear interneurons involved in the metabolism of nitrogen monoxide, hydrogen sulphide and carbon monoxide in the caudal brain stem humans.Methods: The cross-sectional study was performed. We used histochemical and immunohistochemical methods to study the internuclear interneurons expressing neuronal nitric oxide synthase, cystathionine β-synthase and heme oxygenase-2 which are located between the giant and small cell reticular nuclei (cell group 1), small cell reticular nucleus and the nucleus of the solitary tract (cell group 2) or is surrounded by reticular lateral nucleus (cell group 3).Results: The work was carried out on the corpses of 6 men 18–44 years old who died from causes unrelated to the damage of the central nervous system. We revealed the differences between internuclear organization and intranuclear interneurons and local structural features of internuclear interneurons that are more clearly visible between the cell group 1 including a relatively large number of large neurons and cell groups 2 and 3 (р 0,001). In the latter two groups small cells with high concentrations of the neuronal nitric oxide synthase and heme oxygenase-2 dominated.Conclusion: Despite the fact that the number of internuclear interneurons significantly is less than the number of intranuclear cells, they have structural prerequisites to control integration processes in the brain. Internuclear interneurons produce gasotransmitters and classical mediators of nerve impulse, form a local chain of interneurons between vasomotor nuclei, share many links with the above and the lower parts of the brain.

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Neuronal nitric oxide synthase alternatively spliced forms: Prominent functional localizations in the brain

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.94.7.3396 ◽

1997 ◽

Vol 94 (7) ◽

pp. 3396-3401 ◽

Cited By ~ 196

Author(s):

M. J. L. Eliasson ◽

S. Blackshaw ◽

M. J. Schell ◽

S. H. Snyder

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Alternatively Spliced ◽

Oxide Synthase ◽

The Brain

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An enhanced expression of hypothalamic neuronal nitric oxide synthase in a rat model of simulated transport stress

BMC Veterinary Research ◽

10.1186/s12917-019-2071-x ◽

2019 ◽

Vol 15 (1) ◽

Cited By ~ 1

Author(s):

Jia Wang ◽

Jiao Li ◽

Mingyuan Yu ◽

Yuying Wang ◽

Yunfei Ma

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Rat Model ◽

Neuronal Nitric Oxide Synthase ◽

Enhanced Expression ◽

Transport Stress ◽

Oxide Synthase

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Comparative Genomic and Network Analysis of nNOS by Using Different Bioinformatics Approaches

Current Pharmacogenomics and Personalized Medicine ◽

10.2174/1875692118666210616165145 ◽

2021 ◽

Vol 18 ◽

Author(s):

Nymphaea Arora ◽

Vikash Prashar ◽

Tania Arora ◽

Randeep Sidhu ◽

Anshul Mishra ◽

...

Keyword(s):

Nitric Oxide ◽

Network Analysis ◽

Nitric Oxide Synthase ◽

Vascular Tone ◽

Neuronal Nitric Oxide Synthase ◽

Homologous Sequences ◽

Airway Tone ◽

Oxide Synthase ◽

The Brain

Introduction: Nitric oxide (NO) is a diatomic free radical gaseous molecule that is formed from L-arginine through NOS (Nitric oxide synthase) catalyzed reaction. NO controls vascular tone (hence blood pressure), insulin secretion, airway tone, and peristalsis and is involved in angiogenesis (growth of new blood vessels) and in the development of the nervous system. In the CNS, NO is an important messenger molecule, which is involved in various major functions in the brain. NOS has been classified into three isoforms which include nNOS (neuronal NOS), eNOS (endothelial NOS), and iNOS (inducible NOS). NOS1 is localized on chromosome 12, consisting of 1434 amino acids and 161 KDa molecular weight. nNOS is involved in synaptic transmission, regulating the tone of smooth muscles, penile erection. We studied NOS1 gene and protein network analysis through in silico techniques as human nNOS sequence was fetched from GenBank, and its homologous sequences were retrieved through BLAST search. Moreover, the results of this study exploit the role of NOS1 in various pathways, which provide ways to regulate it in various neurodegenerative diseases. Background: Previous research has revealed the role of Nitric Oxide (NO) formed from L-arginine through NOS (Nitric Oxide Synthase) as a physiological inter/intracellular messenger in the central as well as the peripheral nervous system. The diverse functions of NOS include insulin secretion, airway tone, vascular tone regulation, and in the brain, it is involved in differentiation, development, synaptic plasticity, and neurosecretion. Objective: The objective of this study is to unravel the role of neuronal Nitric Oxide Synthase (nNOS) in different pathways and its involvement as a therapeutic target in various neurodegenerative disorders, which can surely provide ways to regulate its activity in different aspects. Materials and Methods: In this study, we employed various bioinformatics tools and databases, initiating the study by fetching the neuronal Nitric Oxide Synthase (nNOS) sequence(GenBank) to find its homologous sequences(BLAST) and then exploring its physical properties and post-translational modifications, enhancing the research by network analysis(STRING), leading to its functional enrichment(Panther). Results : The results positively support the hypothesis of its role in various pathways related to neurodegeneration., Its interacting partners are the probable therapeutic targets of various neurodegenerative diseases focusing on specifically multi-target analysis. Conclusion: This study considered the evolutionary trend of physical, chemical, and biological properties of NOS1 through different phyla. The neuronal Nitric Oxide Synthase (nNOS), being one of the three isoforms of NOS (Nitric Oxide Synthase), is found to be involved in more pathways than just forming Nitric Oxide. This research provides the base for further neurological research.

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Abstract 1333: Modulation Of Cardiac Beta-adrenergic Responsiveness By The Neuronal Nitric Oxide Synthase/Sarcolemmal Calcium Pump Complex

Circulation ◽

10.1161/circ.116.suppl_16.ii_273 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Tamer M Mohamed ◽

Delvac Oceandy ◽

Nasser Alatwi ◽

Florence Baudoin ◽

Elizabeth J Cartwright ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Neuronal Nitric Oxide Synthase ◽

Neonatal Rat ◽

No Production ◽

Adrenergic Stimulation ◽

Rat Cardiomyocytes ◽

Adrenergic Response ◽

Oxide Synthase

The pivotal role of neuronal nitric oxide synthase (nNOS) in regulating cardiac function has only recently been unveiled. Notably, others have shown that responsiveness to β-adrenergic stimulation is dependent on nNOS activity. In a cellular model, we showed that the Ca 2+ /calmodulin-dependent nNOS activity is reduced by overexpression of isoform 4b of the plasma membrane Ca 2+ /Calmodulin-dependent Ca 2+ -pump (PMCA4b), which binds to nNOS. We demonstrated that PMCA4b overexpression in the heart reduced β-adrenergic responsiveness in vivo via an nNOS dependent mechanism (Oceandy et al, Circulation 2007). Here we investigated the cellular mechanisms of the regulation of the β-adrenergic response by PMCA4b. We used an adenoviral system to overexpress PMCA4b (PMCA4b cells) or LacZ (control, C) in neonatal rat cardiomyocytes. PMCA4b cells showed an 18±5% and 24±5% reduction in nitric oxide (DAF-FM fluorescence) and cGMP levels, respectively (n=6, p<0.05 each) compared to C demonstrating the regulation of NO production by the PMCA4b in this system. Since nNOS has been shown to regulate phospholamban (PLB) phosphorylation, we examined phosphorylation of PLB at Ser16. PMCA4b cells showed a significant increase in Ser16-PLB at baseline (66±17%, p<0.05) compared to C. As a result of increased baseline Ser16-PLB in PMCA4b cells, β-adrenergic stimulation of PMCA4b cells using 2μM isoproter-enol (IP) showed reduced relative induction in Ser16-PLB (23±10% vs. 78±19% in C; n=5, p<0.05). Further analysis in adult cardiomyocytes isolated from our PMCA4b transgenic mice (PMCA4b TG) demonstrated that PMCA4b TG showed 3-fold higher Ser16-PLB phosphorylation at baseline compared to wild type (WT) myocytes and the relative response following β-adrenergic stimulation was significantly reduced (1.2±0.2 fold induction after IP treatment in PMCA4b TG, vs. 3.1±0.7 in WT, n=5, p<0.05). Thus, PMCA4b regulates NO production from nNOS, which in turn modulates cGMP levels and PLB phosphorylation. These findings provide mechanistic insight into the regulation of the β-adrenergic response in the heart by PMCA4b and place this Ca 2+ -pump upstream of the recently described pathway linking nNOS and Ser16-PLB phosphorylation and downstream of the β-adrenergic receptor(s).

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