Ethanol Induced Changes in Superoxide Anion and Nitric Oxide in Cultured Microglia

Colton, Carol A.; Snell‐Callanan, Julie; Chernyshev, Olga N.

doi:10.1111/j.1530-0277.1998.tb04315.x

Cited by 38 publications

(23 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cultured neonatal hamster microglia exposed to alcohol for 24-48 h show increased levels of superoxide anions (Colton et al, 1998). Consequently, shifts in oxidative stress can impact neuronal cell viability.…”

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 99%

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

223

170

View full text Add to dashboard Cite

Drugs of abuse cause persistent alterations in synaptic plasticity that may underlie addiction behaviors. Evidence suggests glial cells have an essential and underappreciated role in the development and maintenance of drug abuse by influencing neuronal and synaptic functions in multifaceted ways. Microglia and astrocytes perform critical functions in synapse formation and refinement in the developing brain, and there is growing evidence that disruptions in glial function may be implicated in numerous neurological disorders throughout the lifespan. Linking evidence of function in health and under pathological conditions, this review will outline the glial and neuroimmune mechanisms that may contribute to drug-abuse liability, exploring evidence from opioids, alcohol, and psychostimulants. Drugs of abuse can activate microglia and astrocytes through signaling at innate immune receptors, which in turn influence neuronal function not only through secretion of soluble factors (eg, cytokines and chemokines) but also potentially through direct remodeling of the synapses. In sum, this review will argue that neural-glial interactions represent an important avenue for advancing our understanding of substance abuse disorders.

show abstract

Section: Alcohol Glia and Neuroimmune Signalingmentioning

confidence: 99%

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Lacagnina

Rivera

Bilbo

2016

Neuropsychopharmacol

223

170

View full text Add to dashboard Cite

show abstract

“…Furthermore, Sullivan and Zahr [14] extensively described neuropathological, neuroelectrophysiological, neuropsychological, and neuroradiological evidence for alcohol-induced neuronal loss in humans. We and others have demonstrated the biochemical and molecular mechanisms of alcohol-induced oxidative production as contributing factors to neuronal degeneration after alcohol-induced breaching of brain microvascular endothelial cells [15,16], brain astrocytes [17,18], and cultured microglia [19]. We reported a significant induction of cytochrome P450-2E1 activity, which was associated with increased levels of reactive oxygen species (ROS) and nitric oxide (NO) production in human neurons after exposure to 17.5 mM ethanol (EtOH) [17].…”

mentioning

confidence: 99%

Acetyl-l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

Rump

Muneer

Szlachetka

et al. 2010

Free Radical Biology and Medicine

View full text Add to dashboard Cite

The studies presented here demonstrate the protective effect of acetyl-L-carnitine (ALC) against alcohol-induced oxidative neuroinflammation, neuronal degeneration, and impaired neurotransmission. Our findings reveal the cellular and biochemical mechanisms of alcohol-induced oxidative damage in various types of brain cells. Chronic ethanol administration to mice caused an increase in inducible nitric oxide synthase (iNOS) and 3-nitrotyrosine adduct formation in frontal cortical neurons but not in astrocytes from brains of these animals. Interestingly, alcohol administration caused a rather selective activation of NADPH oxidase (NOX), which, in turn, enhanced levels of reactive oxygen species (ROS) and 4-hydroxynonenal, but these were predominantly localized in astrocytes and microglia. Oxidative damage in glial cells was accompanied by their pronounced activation (astrogliosis) and coincident neuronal loss, suggesting that inflammation in glial cells caused neuronal degeneration. Immunohistochemistry studies indicated that alcohol consumption induced different oxidative mediators in different brain cell types. Thus, nitric oxide was mostly detected in iNOS-expressing neurons, whereas ROS were predominantly generated in NOX-expressing glial cells after alcohol ingestion. Assessment of neuronal activity in ex vivo frontal cortical brain tissue slices from ethanol-fed mice showed a reduction in long-term potentiation synaptic transmission compared with slices from controls. Coadministration of ALC with alcohol showed a significant reduction in oxidative damage and neuronal loss and a restoration of synaptic neurotransmission in this brain region, suggesting that ALC protects brain cells from ethanol-induced oxidative injury. These findings suggest the potential clinical utility of ALC as a neuroprotective agent that prevents alcohol-induced brain damage and development of neurological disorders.

show abstract

“…Correlation between oxidative and inflammatory biomarkers has not been achieved in the AD brain, although the activation of an inflammatory response might, in large part, explain AD brain oxidation. For instance, activated microglia release superoxide (O 2 ⅐ Ϫ ) and hydrogen peroxide (H 2 O 2 ) (Colton et al, 1994), whereas astrocytes and microglia stimulated with appropriate cytokines or ␤-amyloid peptides (A␤) express inducible nitric oxide synthase (iNOS) and generate nitric oxide-derived species, including peroxynitrite (ONOO Ϫ ) (Beckman et al, 1994;Goodwin et al, 1995;Li et al, 1996;Hensley et al, 1997).In the present study HPLC with electrochemical array detection (HPLC-ECD) was used to quantify discrete tyrosine oxidation products expected to form during an inflammatory response. Tyrosine (Tyr), 3-nitrotyrosine (3-NO 2 -Tyr), and 3,3Ј-dityrosine (diTyr) were determined simultaneously in the protein digests of brain specimens obtained from AD and neuropathologically normal subjects.…”

mentioning

confidence: 99%

Electrochemical Analysis of Protein Nitrotyrosine and Dityrosine in the Alzheimer Brain Indicates Region-Specific Accumulation

et al. 1998

View full text Add to dashboard Cite

HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3Ј-dityrosine (diTyr) and 3-nitrotyrosine (3-NO 2 -Tyr) in four regions of the human brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3-NO 2 -Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching quantities five-to eightfold greater than mean concentrations in brain and VF of cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was decreased globally in the AD brain and VF. The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.Key words: HPLC; nitrotyrosine; dityrosine; Alzheimer's disease; protein oxidation; inflammation The Alzheimer's disease (AD) brain exhibits region-specific patterns of amyloid plaque deposition, neurofibrillary tangle (NFT) accumulation, and neuron death. The limbic system and association areas of the neocortex show the most pronounced histopathological alterations in AD, whereas cortical somatosensory and cerebellar neurons are relatively spared (Pearson et al., 1985;Henderson and Finch, 1989;Braak and Braak, 1994). Recent models of AD attempt to link disease progression with an inflammatory component combined with increased oxidative stress (Rogers et al., 1996). C lassical hallmarks of inflammation such as edema and neutrophil infiltration are not acknowledged characteristics of the AD brain, although numerous correlates of inflammation are present. Acute-phase reactants such as C-reactive protein, major histocompatibility complex glycoproteins, complement, monocyte chemoattractants, interleukin-1, and interleukin-6 are elevated in AD brain in spatial association with neuritic plaques (Griffin et al., 1989McGeer et al., 1989;Bauer et al., 1991;Strauss et al., 1992;C arpenter et al., 1993; Wood et al., 1993;Iwamoto et al., 1994;Mrak et al., 1995;Pereira et al., 1996;Rogers et al., 1996;Sheng et al., 1996). Reactive microglia, f unctionally similar to monocytes, are increased in the AD brain and concentrate near senile plaques (McGeer et al., 1987;Haga et al., 1989;Itagaki et al., 1989; Carpenter et al., 1993;MacKenzie et al., 1995).Enhanced oxidative stress in the AD brain is manifested by increases in protein carbonyl content and lipid and DNA oxidation products and by inactivation of sensitive enzymes (Oliver et al., 1987;C. Smith et al., 1991C. Smith et al., , 1992Mecocci et al., 1993;Balazs and Leon, 1994;Chen et al., 1994;Hensley et al., 1995; Lovell et al., 1995;M. Smith et al., 1996;Butterfield et al., 1997;Lyras et al., 1997;Sayre et al., 1997). Correlation between oxidative and inflammatory biomarkers has not been achieved in the AD brain, although the activation of an inflammatory response might, in large part, explain AD brain oxidation. For instance, activated microglia release superoxide (O 2 ⅐ Ϫ ) and hydrogen peroxide (H 2 O 2 ) (Colton et al., 1994), whe...

show abstract

Ethanol Induced Changes in Superoxide Anion and Nitric Oxide in Cultured Microglia

Cited by 38 publications

References 54 publications

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

Acetyl-l-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain

Electrochemical Analysis of Protein Nitrotyrosine and Dityrosine in the Alzheimer Brain Indicates Region-Specific Accumulation

Contact Info

Product

Resources

About