Neurodegeneration by activated microglia across a nanofiltration membrane

Graber, David J.; Snyder-Keller, Abigail; Lawrence, David A.; Turner, James N.

doi:10.1002/jbt.20384

Cited by 9 publications

(7 citation statements)

References 32 publications

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“…Moreover it has been demonstrated that nitric oxide caused neuronal death not only via NMDA receptors, but it could also act directly upon immature neurons, through a not fully defined mechanism [111]. Recently, Graber et al ., [112] further supported NO production as an important mediator in microglia-induced neuron death. Damaging actions of NO, mostly mediated by microglia activation, have been extensively considered in recent reviews [113, 114].…”

Section: Nitric Oxide In the Cross-talk Between Microglia And Neuronsmentioning

confidence: 94%

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

Contestabile¹,

Monti²,

Polazzi³

2012

Current Neuropharmacology

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Nitric oxide (NO) is a versatile cellular messenger performing a variety of physiologic and pathologic actions in most tissues. It is particularly important in the nervous system, where it is involved in multiple functions, as well as in neuropathology, when produced in excess. Several of these functions are based on interactions between NO produced by neurons and NO produced by glial cells, mainly astrocytes and microglia. The present paper briefly reviews some of these interactions, in particular those involved in metabolic regulation, control of cerebral blood flow, axonogenesis, synaptic function and neurogenesis. Aim of the paper is mainly to underline the physiologic aspects of these interactions rather than the pathologic ones.

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Section: Nitric Oxide In the Cross-talk Between Microglia And Neuronsmentioning

confidence: 94%

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

Contestabile¹,

Monti²,

Polazzi³

2012

Current Neuropharmacology

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“…Moreover, excessive microglial production of NO induced by UCB in hippocampal slices (Silva et al, 2012) may lead to increased cell death. In fact, and in contrast to the “protective” effects exerted by microglia in preventing excessive glutamate, microglia additionally contribute to the generation of NO, an important mediator in microglia-induced neuron death (Golde et al, 2002; Graber et al, 2012). Generation of NO may derive from iNOS activation, which once activated produces moderate levels of NO chronically without any requirement for further activation (Brown, 2010), or from constitutive NOS, probably originating in the case of UCB an overproduction that may inhibit phagocytosis (Kopec and Carroll, 2000), as we observed following the 4 h of incubation (Silva et al, 2010).…”

Section: Microglia In the Process Of Bilirubin-induced Inflammationmentioning

confidence: 99%

The Evolving Landscape of Neurotoxicity by Unconjugated Bilirubin: Role of Glial Cells and Inflammation

Brites¹

2012

Front. Pharmacol.

115

103

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Unconjugated hyperbilirubinemia is a common condition in the first week of postnatal life. Although generally harmless, some neonates may develop very high levels of unconjugated bilirubin (UCB), which may surpass the protective mechanisms of the brain in preventing UCB accumulation. In this case, both short-term and long-term neurodevelopmental disabilities, such as acute and chronic UCB encephalopathy, known as kernicterus, or more subtle alterations defined as bilirubin-induced neurological dysfunction (BIND) may be produced. There is a tremendous variability in babies’ vulnerability toward UCB for reasons not yet explained, but preterm birth, sepsis, hypoxia, and hemolytic disease are comprised as risk factors. Therefore, UCB levels and neurological abnormalities are not strictly correlated. Even nowadays, the mechanisms of UCB neurotoxicity are still unclear, as are specific biomarkers, and little is known about lasting sequelae attributable to hyperbilirubinemia. On autopsy, UCB was shown to be within neurons, neuronal processes, and microglia, and to produce loss of neurons, demyelination, and gliosis. In isolated cell cultures, UCB was shown to impair neuronal arborization and to induce the release of pro-inflammatory cytokines from microglia and astrocytes. However, cell dependent sensitivity to UCB toxicity and the role of each nerve cell type remains not fully understood. This review provides a comprehensive insight into cell susceptibilities and molecular targets of UCB in neurons, astrocytes, and oligodendrocytes, and on phenotypic and functional responses of microglia to UCB. Interplay among glia elements and cross-talk with neurons, with a special emphasis in the UCB-induced immunostimulation, and the role of sepsis in BIND pathogenesis are highlighted. New and interesting data on the anti-inflammatory and antioxidant activities of different pharmacological agents are also presented, as novel and promising additional therapeutic approaches to BIND.

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“…Nitric oxide also participates in the interrelationships between neurons and gliacytes. 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 ).…”

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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Neurodegeneration by activated microglia across a nanofiltration membrane

Cited by 9 publications

References 32 publications

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

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

The Evolving Landscape of Neurotoxicity by Unconjugated Bilirubin: Role of Glial Cells and Inflammation

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

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