Neuronal-glial Interactions Define the Role of Nitric Oxide in Neural Functional Processes

Contestabile, Antonio; Monti, Barbara; Polazzi, Elisabetta

doi:10.2174/157015912804143522

Cited by 23 publications

(15 citation statements)

References 130 publications

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“…NO is a versatile molecule particularly important in the CNS, where it participates in synaptic plasticity, neurotransmitter release, and also in immune response. However, when produced in excess via iNOS by activated microglia, NO contributes to acute and chronic inflammation and causes neuronal cell death, directly or by its oxidation products, such as peroxynitrite, which is produced by the oxidation of NO with superoxide [63][64][65][66][67]. Elevated levels of pro-inflammatory cytokines, such as TNF-α, IFN-γ, IL-1β, IL-6, and IL-18, have also been shown in various inflammatory conditions and, in this regard, a recent study showed that the microalga Euglena tuba can counteract the increased levels of inflammatory cytokines in an LPS-induced model of systemic inflammation [27].…”

Section: Discussionmentioning

confidence: 99%

Carotenoid Extract Derived from Euglena gracilis Overcomes Lipopolysaccharide-Induced Neuroinflammation in Microglia: Role of NF-κB and Nrf2 Signaling Pathways

et al. 2021

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Activation of microglia results in the increased production and release of a series of inflammatory and neurotoxic mediators, which play essential roles in structural and functional neuronal damage and in the development and progression of a number of neurodegenerative diseases. The microalga Euglena gracilis (Euglena), rich in vitamins, minerals, and other nutrients, has gained increasing attention due to its antimicrobial, anti-viral, antitumor, and anti-inflammatory activities. In particular, anti-inflammatory properties of Euglena could exert neuroprotective functions in different neurodegenerative diseases related to inflammation. However, the mechanisms underlying the anti-inflammatory effect of Euglena are not fully understood. In this study, we investigated whether Euglena could attenuate microglia activation and we also studied the mechanism of its anti-inflammatory activity. Our results showed that non-cytotoxic concentrations of a Euglena acetone extract (EAE) downregulated the mRNA expression levels and release of pro-inflammatory mediators, including NO, IL-1β, and TNF-α in LPS-stimulated microglia. EAE also significantly blocked the LPS-induced nuclear translocation of NF-κB p65 subunit and increased the mRNA expression of nuclear factor erythroid 2–related factor (Nrf2) and heme oxygenase-1 (HO-1). Furthermore, the release of pro-inflammatory mediators and NF-κB activation were also blocked by EAE in the presence of ML385, a specific Nrf2 inhibitor. Together, these results show that EAE overcomes LPS-induced microglia pro-inflammatory responses through downregulation of NF-κB and activation of Nrf2 signaling pathways, although the two pathways seem to get involved in an independent manner.

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Section: Discussionmentioning

confidence: 99%

Carotenoid Extract Derived from Euglena gracilis Overcomes Lipopolysaccharide-Induced Neuroinflammation in Microglia: Role of NF-κB and Nrf2 Signaling Pathways

et al. 2021

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“…It was shown that increased synthesis of NO by microglia can lead to damage of neurons (Graber et al, 2012 ). iNOS is responsible for synthesis of nitric oxide in microglia (Contestabile et al, 2012 ). In vitro studies indicated NO-dependent microglial reactions in the form of death of neurons, especially under conditions of inflammation (Graber et al, 2012 ).…”

Section: Nitric Oxide In Pathogenesis Of Schizophreniamentioning

confidence: 99%

Role of nitric oxide and related molecules in schizophrenia pathogenesis: biochemical, genetic and clinical aspects

et al. 2015

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Currently, schizophrenia is considered a multifactorial disease. Over the past 50 years, many investigators have considered the role of toxic free radicals in the etiology of schizophrenia. This is an area of active research which is still evolving. Here, we review the recent data and current concepts on the roles of nitric oxide (NO) and related molecules in the pathogenesis of schizophrenia. NO is involved in storage, uptake and release of mediators and neurotransmitters, including glutamate, acetylcholine, noradrenaline, GABA, taurine and glycine. In addition, NO diffuses across cell membranes and activates its own extrasynaptic receptors. Further, NO is involved in peroxidation and reactive oxidative stress. Investigations reveal significant disturbances in NO levels in the brain structures (cerebellum, hypothalamus, hippocampus, striatum) and fluids of subjects with schizophrenia. Given the roles of NO in central nervous system development, these changes may result in neurodevelopmental changes associated with schizophrenia. We describe here the recent literature on NOS gene polymorphisms on schizophrenia, which all point to consistent results. We also discuss how NO may be a new target for the therapy of mental disorders. Currently there have been 2 randomized double-blind placebo-controlled trials of L-lysine as an NOS inhibitor in the CNS.

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“…However, a full understanding of brain's physics and biochemistry comes not only from an integrated analysis of the cells within their networks, but also from the interactions of and feedback among the networks. Although in recent years studies on biochemical interactions among brain's networks have started to emerge [1][2][3][4][5][6][7], a good comprehension of the coupled mechano-electrochemical processes that either provide or diminish brain's functions is still lacking. This knowledge is critical in improving existing diagnostic and therapeutic protocols and developing better new ones.…”

Section: -Introductionmentioning

confidence: 99%

“…Figure 1 shows a schematic of those aspects of the neuro-glial-vascular unit that are of interest to this paper. A neuro-glial-vascular unit (also known in the literature as neurovascular unit) is made of a group of neurons and nearby astrocytes (glial cells) that are connected functionally to the endothelium and smooth muscles of the small blood vessels with the purpose of controlling the supply of cerebral blood needed for the proper functionality of the brain [2]. Astrocytes have at least one endfoot that is in contact with the vasculature, and it is believed that the endfeet of all astrocytes completely encompass all the cerebral vessels [4].…”

Section: -Introductionmentioning

confidence: 99%

“…Two isoforms are 2+dependent and are expressed in the neurons (nNO) and in the vascular endothelium and choroid plexus (eNO) [14]. The third isoform is inducible and independent of calcium (iNO) and is expressed in macrophages, glial cells, and tumour cells in response to insults such as ischemia and neuroinflammation [2,14]. Endothelial NO maintains cerebral microcirculation by inhibiting platelet aggregation, leukocyte adhesion and migration, and reducing the blood pressure and the proliferation of the vascular smooth muscle.…”

Section: -Introductionmentioning

confidence: 99%

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Mathematical Modeling of a Brain-on-a-Chip: A Study of the Neuronal Nitric Oxide Role in Cerebral Microaneurysms

Drapaca

2018

Emerg Sci J

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Brain tissue is a complex material made of interconnected neural, glial, and vascular networks. While the physics and biochemistry of brain’s cell types and their interactions within their networks have been studied extensively, only recently the interactions of and feedback among the networks have started to capture the attention of the research community. Thus, a good understanding of the coupled mechano-electrochemical processes that either provide or diminish brain’s functions is still lacking. One way to increase the knowledge on how the brain yields its functions is by developing a robust controlled feedback engineering system that uses fundamental science concepts to guide and interpret experiments investigating brain’s response to various stimuli, aging, trauma, diseases, treatment and recovery processes. Recently, a mathematical model for an implantable neuro-glial-vascular unit, named brain-on-a-chip, was proposed that can be optimized to perform some fundamental cellular processes that could facilitate monitoring and supporting brain’s functions, and highlight basic brain mechanisms. In this paper we use coupled elastic, viscoelastic and mass elements to model a brain-on-a-chip made of a neuron and its membrane, and astrocyte’s endfeet connected to an arteriole’s wall. We propose two constrained Lagrangian formulations that link the Hodgkin-Huxley model of the neuronal membrane, and the mechanics of the neuron, neuronal membrane, and the glia’s endfeet. The effects of the nitric oxide produced by neurons and endothelial cells on the proposed brain-on-a-chip are investigated through numerical simulations. Our numerical simulations suggest that a non-decaying synthesis of nitric oxide may contribute to the onset of a cerebral microaneurysm.

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Neuronal-glial Interactions Define the Role of Nitric Oxide in Neural Functional Processes

Cited by 23 publications

References 130 publications

Carotenoid Extract Derived from Euglena gracilis Overcomes Lipopolysaccharide-Induced Neuroinflammation in Microglia: Role of NF-κB and Nrf2 Signaling Pathways

Carotenoid Extract Derived from Euglena gracilis Overcomes Lipopolysaccharide-Induced Neuroinflammation in Microglia: Role of NF-κB and Nrf2 Signaling Pathways

Role of nitric oxide and related molecules in schizophrenia pathogenesis: biochemical, genetic and clinical aspects

Mathematical Modeling of a Brain-on-a-Chip: A Study of the Neuronal Nitric Oxide Role in Cerebral Microaneurysms

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