The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Melvyn P. Heyes - One of the best experts on this subject based on the ideXlab platform.
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Quinolinic Acid is extruded from the brain by a probenecid sensitive carrier system a quantitative analysis
Journal of Neurochemistry, 2008Co-Authors: Paul F Morrison, Gregory M Morishige, Karen E Beagles, Melvyn P. HeyesAbstract:Abstract: Although the neurotoxic tryptophan-kynurenine pathway metabolite Quinolinic Acid originates in brain by both local de novo synthesis and entry from blood, its concentrations in brain parenchyma, extracellular fluid, and CSF are normally below blood values. In the present study, an intraperitoneal injection of probenecid (400 mg/kg), an established inhibitor of Acid metabolite transport in brain, into gerbils, increased Quinolinic Acid concentrations in striatal homogenates, CSF, serum, and homogenates of kidney and liver. Direct administration of probenecid (10 mM) into the brain compartment via an in vivo microdialysis probe implanted into the striatum also caused a progressive elevation in both Quinolinic Acid and homovanillic Acid concentrations in the extracellular fluid compartment but was without effect on serum Quinolinic Acid levels. A model of microdialysis transport showed that the elevations in extracellular fluid Quinolinic Acid and homovanillic Acid levels following intrastriatal application are consistent with probenecid block of a microvascular Acid transport mechanism. We conclude that Quinolinic Acid in brain is maintained at concentrations below blood levels largely by active extrusion via a probenecid-sensitive carrier system.
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elevated cerebrospinal fluid Quinolinic Acid levels are associated with region specific cerebral volume loss in hiv infection
Brain, 2001Co-Authors: Melvyn P. Heyes, Ronald J Ellis, Lee Ryan, Meredith E Childers, Igor Grant, Tanya Wolfson, Sarah L Archibald, Terry L JerniganAbstract:Neuronal injury, dendritic loss and brain atrophy are frequent complications of infection with human immunodeficiency virus (HIV) type 1. Activated brain macrophages and microglia can release Quinolinic Acid, a neurotoxin and NMDA (N-methyl-D-aspartate) receptor agonist, which we hypothesize contributes to neuronal injury and cerebral volume loss. In the present cross-sectional study of 94 HIV-1-infected patients, elevated CSF Quinolinic Acid concentrations correlated with worsening brain atrophy, quantified by MRI, in regions vulnerable to excitotoxic injury (the striatum and limbic cortex) but not in regions relatively resistant to excitotoxicity (the non-limbic cortex, thalamus and white matter). Increased CSF Quinolinic Acid concentrations also correlated with higher CSF HIV-1 RNA levels. In support of the specificity of these associations, blood levels of Quinolinic Acid were unrelated to striatal and limbic volumes, and CSF levels of beta(2)-microglobulin, a non-specific and non-excitotoxic marker of immune activation, were unrelated to regional brain volume loss. These results are consistent with the hypothesis that Quinolinic Acid accumulation in brain tissue contributes to atrophy in vulnerable brain regions in HIV infection and that virus replication is a significant driver of local Quinolinic Acid biosynthesis.
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Quinolinic Acid in the cerebrospinal fluid of children after traumatic brain injury.
Critical care medicine, 1999Co-Authors: Michael J. Bell, Melvyn P. Heyes, Patrick M. Kochanek, Stephen R. Wisniewski, Elisabeth H. Sinz, Robert S. B. Clark, Andrew R. Blight, Donald W. Marion, P. David AdelsonAbstract:OBJECTIVE To measure Quinolinic Acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF Quinolinic Acid concentrations to clinically important variables. DESIGN A prospective, observational study. SETTING The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university-based children's hospital. PATIENTS Seventeen critically ill children following severe TBI (Glasgow Coma Scale score
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Sources of the neurotoxin Quinolinic Acid in the brain of HIV-1-infected patients and retrovirus-infected macaques
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 1998Co-Authors: Melvyn P. Heyes, Kuniaki Saito, Andrew A. Lackner, Clayton A. Wiley, Cristian L. Achim, Sanford P MarkeyAbstract:This study investigated the sources of Quinolinic Acid, a neurotoxic tryptophan–kynurenine pathway metabolite, in the brain and blood of HIV-infected patients and retrovirus-infected macaques. In brain, Quinolinic Acid concentrations in HIV-infected patients were elevated by >300-fold to concentrations that exceeded cerebrospinal fluid (CSF) by 8.9-fold. There were no significant correlations between elevated serum Quinolinic Acid levels with those in CSF and brain parenchyma. Because nonretrovirus-induced encephalitis confounds the interpretation of human postmortem data, rhesus macaques infected with retrovirus were used to examine the mechanisms of increased Quinolinic Acid accumulations and determine the relationships of Quinolinic Acid to encephalitits and systemic responses. The largest kynurenine pathway responses in brain were associated with encephalitis and were independent of systemic responses. CSF Quinolinic Acid levels were also elevated in all infected macaques, but particularly those with ...
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Quinolinic Acid in patients with systemic lupus erythematosus and neuropsychiatric manifestations
The Journal of rheumatology, 1996Co-Authors: Scott A. Vogelgesang, Melvyn P. Heyes, Sterling G. West, Andres M. Salazar, P.p. Sfikakis, Robert N. Lipnick, Gary Klipple, George C. TsokosAbstract:Objective. To evaluate the relationship between Quinolinic Acid, a neuroactive metabolite of L-tryptophan, and neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Methods. Forty specimens of cerebrospinal fluid (CSF) were obtained from 39 patients with SLE who were evaluated for 40 episodes of neuropsychiatric dysfunction. The diagnosis of the neuropsychiatric dysfunction was determined clinically. CSF and serum specimens were analyzed for levels of Quinolinic Acid without knowledge of the clinical diagnosis. Results. Neuropsychiatric dysfunction attributed to SLE (NPSLE) was confirmed in 30 patient-episodes (Group 1), whereas in the other 10 (Group 2) other etiologies were felt to explain their CNS dysfunction. The median levels of CSF Quinolinic Acid for Group 1 (232.5 nmol/l) were significantly higher than those for Group 2 (median 38.2 nmol/l) (p < 0.014). CSF and serum Quinolinic Acid levels correlated significantly (p < 0.003) but there was no correlation between CSF Quinolinic Acid and CSF protein concentrations or white blood cell counts. Conclusion. We conclude that elevated Quinolinic Acid levels in the CSF and serum may be associated with NPSLE and could possibly play a role in its pathogenesis.
Santy Daya - One of the best experts on this subject based on the ideXlab platform.
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17β-Estradiol Attenuates Quinolinic Acid Insult in the Rat Hippocampus
Metabolic Brain Disease, 2001Co-Authors: Paula Heron, Santy DayaAbstract:A number of studies have shown that 17β-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17β-estradiol against Quinolinic-Acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17β-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 μmol Quinolinic Acid in 2 μL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM–5 μM 17β-estradiol or Quinolinic Acid. The results show that 17β-estradiol protects hippocampal neurons from Quinolinic-Acid-induced neurodegeneration by competing with Quinolinic Acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.
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17Beta-estradiol attenuates Quinolinic Acid insult in the rat hippocampus.
Metabolic brain disease, 2001Co-Authors: Paula Heron, Santy DayaAbstract:A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against Quinolinic-Acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol Quinolinic Acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM-5 microM 17beta-estradiol or Quinolinic Acid. The results show that 17beta-estradiol protects hippocampal neurons from Quinolinic-Acid-induced neurodegeneration by competing with Quinolinic Acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.
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17β-Estradiol Protects Against Quinolinic Acid-Induced Lipid Peroxidation in the Rat Brain
Metabolic Brain Disease, 2000Co-Authors: Paula Heron, Santy DayaAbstract:The neurotoxin Quinolinic Acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17β-estradiol on lipid peroxidation induced by Quinolinic Acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 μg 17β-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 μmol Quinolinic Acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric Acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with Quinolinic Acid alone or in combination with 17β-estradiol. Quinolinic Acid increased lipid peroxidation in a dose dependent manner in vitro , while homogenate co-treated with 17β-estradiol showed a significant reduction in lipid peroxidation. 17β-estradiol was also shown to be protective against Quinolinic Acid in vivo . These results could explain the neuroprotective effect of 17β-estradiol.
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17Beta-estradiol protects against Quinolinic Acid-induced lipid peroxidation in the rat brain.
Metabolic brain disease, 2000Co-Authors: Paula Heron, Santy DayaAbstract:The neurotoxin Quinolinic Acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17β-estradiol on lipid peroxidation induced by Quinolinic Acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 μg 17β-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 μmol Quinolinic Acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric Acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with Quinolinic Acid alone or in combination with 17β-estradiol. Quinolinic Acid increased lipid peroxidation in a dose dependent manner in vitro, while homogenate co-treated with 17β-estradiol showed a significant reduction in lipid peroxidation. 17β-estradiol was also shown to be protective against Quinolinic Acid in vivo. These results could explain the neuroprotective effect of 17β-estradiol.
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Melatonin Reduces Quinolinic Acid-Induced Lipid Peroxidation in Rat Brain Homogenate
Metabolic brain disease, 1999Co-Authors: Garrick Southgate, Santy DayaAbstract:The protective effects of melatonin against the neurotoxin, Quinolinic Acid, were investigated in rat brain homogenate using the thiobarbituric Acid assay. Quinolinic Acid increased lipid peroxidation in a dose dependent manner. When homogenate was co-treated with melatonin there was a significant decrease in lipid peroxidation. The results of the present report show that melatonin may play a protective role in the brain against the neurohormone Quinolinic Acid, which has been identified as a causative agent in Huntington's Disease.
Gilles J. Guillemin - One of the best experts on this subject based on the ideXlab platform.
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Quinolinic Acid toxicity on oligodendroglial cells: relevance for multiple sclerosis and therapeutic strategies.
Journal of neuroinflammation, 2014Co-Authors: Gayathri Sundaram, Bruce J. Brew, Simon Jones, Seray Adams, Chai K. Lim, Gilles J. GuilleminAbstract:The excitotoxin Quinolinic Acid, a by-product of the kynurenine pathway, is known to be involved in several neurological diseases including multiple sclerosis (MS). Quinolinic Acid levels are elevated in experimental autoimmune encephalomyelitis rodents, the widely used animal model of MS. Our group has also found pathophysiological concentrations of Quinolinic Acid in MS patients. This led us to investigate the effect of Quinolinic Acid on oligodendrocytes; the main cell type targeted by the autoimmune response in MS. We have examined the kynurenine pathway (KP) profile of two oligodendrocyte cell lines and show that these cells have a limited threshold to catabolize exogenous Quinolinic Acid. We further propose and demonstrate two strategies to limit Quinolinic Acid gliotoxicity: 1) by neutralizing Quinolinic Acid’s effects with anti-Quinolinic Acid monoclonal antibodies and 2) directly inhibiting Quinolinic Acid production from activated monocytic cells using specific KP enzyme inhibitors. The outcome of this study provides a new insight into therapeutic strategies for limiting Quinolinic Acid-induced neurodegeneration, especially in neurological disorders that target oligodendrocytes, such as MS.
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the endogenous tryptophan metabolite and nad precursor Quinolinic Acid confers resistance of gliomas to oxidative stress
Cancer Research, 2013Co-Authors: Felix Sahm, Gilles J. Guillemin, Seray Adams, Iris Oezen, Christiane A. Opitz, Bernhard Radlwimmer, Andreas Von Deimling, Tilman Ahrendt, Helge B. Bode, Wolfgang WickAbstract:Quinolinic Acid is a product of tryptophan degradation and may serve as a precursor for NAD(+), an important enzymatic cofactor for enzymes such as the DNA repair protein PARP. Pathologic accumulation of Quinolinic Acid has been found in neurodegenerative disorders including Alzheimer and Huntington disease, where it is thought to be toxic for neurons by activating the N-methyl-D-aspartate (NMDA) receptor and inducing excitotoxicity. Although many tumors including gliomas constitutively catabolize tryptophan, it is unclear whether Quinolinic Acid is produced in gliomas and whether it is involved in tumor progression. Here, we show that Quinolinic Acid accumulated in human gliomas and was associated with a malignant phenotype. Quinolinic Acid was produced by microglial cells, as expression of the Quinolinic Acid-producing enzyme 3-hydroxyanthranilate oxygenase (3-HAO) was confined to microglia in glioma tissue. Human malignant glioma cells, but not nonneoplastic astrocytes, expressed Quinolinic Acid phosphoribosyltransferase (QPRT) to use Quinolinic Acid for NAD(+) synthesis and prevent apoptosis when de novo NAD(+) synthesis was blocked. Oxidative stress, temozolomide, and irradiation induced QPRT in glioma cells. QPRT expression increased with malignancy. In recurrent glioblastomas after radiochemotherapy, QPRT expression was associated with a poor prognosis in two independent datasets. Our data indicate that neoplastic transformation in astrocytes is associated with a QPRT-mediated switch in NAD(+) metabolism by exploiting microglia-derived Quinolinic Acid as an alternative source of replenishing intracellular NAD(+) pools. The elevated levels of QPRT expression increase resistance to oxidative stress induced by radiochemotherapy, conferring a poorer prognosis. These findings have implications for therapeutic approaches inducing intracellular NAD(+) depletion, such as alkylating agents or direct NAD(+) synthesis inhibitors, and identify QPRT as a potential therapeutic target in malignant gliomas.
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The Endogenous Tryptophan Metabolite and NAD+ Precursor Quinolinic Acid Confers Resistance of Gliomas to Oxidative Stress
Cancer research, 2013Co-Authors: Felix Sahm, Gilles J. Guillemin, Seray Adams, Iris Oezen, Christiane A. Opitz, Bernhard Radlwimmer, Andreas Von Deimling, Tilman Ahrendt, Helge B. Bode, Wolfgang WickAbstract:Quinolinic Acid is a product of tryptophan degradation and may serve as a precursor for NAD + , an important enzymatic cofactor for enzymes such as the DNA repair protein PARP. Pathologic accumulation of Quinolinic Acid has been found in neurodegenerative disorders including Alzheimer and Huntington disease, where it is thought to be toxic for neurons by activating the N-methyl-D-aspartate (NMDA) receptor and inducing excitotoxicity. Although many tumors including gliomas constitutively catabolize tryptophan, it is unclear whether Quinolinic Acid is produced in gliomas and whether it is involved in tumor progression. Here, we show that Quinolinic Acid accumulated in human gliomas and was associated with a malignant phenotype. Quinolinic Acid was produced by microglial cells, as expression of the Quinolinic Acid-producing enzyme 3-hydroxyanthranilate oxygenase (3-HAO) was confined to microglia in glioma tissue. Human malignant glioma cells, but not nonneoplastic astrocytes, expressed Quinolinic Acid phosphoribosyltransferase (QPRT) to use Quinolinic Acid for NAD + synthesis and prevent apoptosis when de novo NAD + synthesis was blocked. Oxidative stress, temozolomide, and irradiation induced QPRT in glioma cells. QPRT expression increased with malignancy. In recurrent glioblastomas after radiochemotherapy, QPRT expression was associated with a poor prognosis in two independent datasets. Our data indicate that neoplastic transformation in astrocytes is associated with a QPRT-mediated switch in NAD + metabolism by exploiting microglia-derived Quinolinic Acid as an alternative source of replenishing intracellular NAD + pools. The elevated levels of QPRT expression increase resistance to oxidative stress induced by radiochemotherapy, conferring a poorer prognosis. These findings have implications for therapeutic approaches inducing intracellular NAD + depletion, such as alkylating agents or direct NAD + synthesis inhibitors, and identify QPRT as a potential therapeutic target in malignant gliomas. Cancer Res; 73(11); 3225–34. ©2013 AACR .
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Quinolinic Acid: neurotoxicity
The FEBS journal, 2012Co-Authors: Gilles J. GuilleminAbstract:This minireview series reviews some of the most recent findings about Quinolinic Acid's cellular toxicity and its implications in diseases such as HIV associated neurocognitive disorders, depressive disorders and schizophrenia, and finally therapeutic strategies with drugs able to interfere with Quinolinic Acid production and/or effects.
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Chronic exposure of human neurons to Quinolinic Acid results in neuronal changes consistent with AIDS dementia complex.
AIDS (London England), 1998Co-Authors: Stephen J. Kerr, Gilles J. Guillemin, Patricia J. Armati, Bruce J. BrewAbstract:Objective: Concentrations of Quinolinic Acid, an N-methyl-D-aspartate agonist, are often elevated for long periods of time in the cerebrospinal fluid (CSF) and brain tissue of patients with AIDS dementia complex (ADC). This study was designed to test the hypothesis that chronic exposure of human neurons to Quinolinic Acid levels equivalent to those in the CSF of ADC patients is neurotoxic. Design and methods: Human fetal brain 14-16 weeks post-menses was cultured in medium with no detectable levels of Quinolinic Acid. After 4 weeks, 350 or 1200 nmol/l Quinolinic Acid was added to the feeding medium for a further 5 weeks. Neurotoxicity was evaluated using immunohistochemistry, transmission and scanning electron microscopy, and image analysis. Results: A total of 1200 nmol/l Quinolinic Acid caused altered cell associations, a decrease in cell density and decreased microtubule-associated protein (MAP)-2 immunoreactivity compared with cultures exposed to 350 nmol/l Quinolinic Acid or controls. Image analysis of neurons in randomly selected fields revealed significantly swollen cells (P < 0.0001) compared with those treated with 350 nmol/l Quinolinic Acid or controls. Dendritic varicosities and discontinuous microtubular arrays were present in neurons exposed to both Quinolinic Acid concentrations, but not in control cultures. Conclusions: This study is the first to assess Quinolinic Acid levels in the experimental medium, and demonstrates that chronic exposure of human neurons to concentrations of Quinolinic Acid equivalent to those in the CSF of patients with ADC leads to alterations in dendritic ultrastructure and MAP-2 immunoreactivity, which is consistent with ADC pathology.
Paula Heron - One of the best experts on this subject based on the ideXlab platform.
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17β-Estradiol Attenuates Quinolinic Acid Insult in the Rat Hippocampus
Metabolic Brain Disease, 2001Co-Authors: Paula Heron, Santy DayaAbstract:A number of studies have shown that 17β-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17β-estradiol against Quinolinic-Acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17β-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 μmol Quinolinic Acid in 2 μL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM–5 μM 17β-estradiol or Quinolinic Acid. The results show that 17β-estradiol protects hippocampal neurons from Quinolinic-Acid-induced neurodegeneration by competing with Quinolinic Acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.
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17Beta-estradiol attenuates Quinolinic Acid insult in the rat hippocampus.
Metabolic brain disease, 2001Co-Authors: Paula Heron, Santy DayaAbstract:A number of studies have shown that 17beta-estradiol has neuroprotective properties. In this study the neuroprotective effect of 17beta-estradiol against Quinolinic-Acid-induced neuronal damage was investigated. Ovariectomized rats were separated into three groups of five animals each. Rats received daily subcutaneous injections of either olive oil or 17beta-estradiol in olive oil for 7 days prior to and following a single intrahippocampal injection of 1 micromol Quinolinic Acid in 2 microL phosphate-buffered saline. The brains were removed and the hippocampi either sectioned and stained for microscopic examination or used in glutamate receptor saturation binding studies. Glutamate receptor displacement binding studies were also performed using concentrations of 0.05 nM-5 microM 17beta-estradiol or Quinolinic Acid. The results show that 17beta-estradiol protects hippocampal neurons from Quinolinic-Acid-induced neurodegeneration by competing with Quinolinic Acid to bind to the N-methyl-D-aspartate (NMDA) receptor. This would result in a decrease in intracellular free-calcium influx and resultant neuronal swelling.
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17β-Estradiol Protects Against Quinolinic Acid-Induced Lipid Peroxidation in the Rat Brain
Metabolic Brain Disease, 2000Co-Authors: Paula Heron, Santy DayaAbstract:The neurotoxin Quinolinic Acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17β-estradiol on lipid peroxidation induced by Quinolinic Acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 μg 17β-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 μmol Quinolinic Acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric Acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with Quinolinic Acid alone or in combination with 17β-estradiol. Quinolinic Acid increased lipid peroxidation in a dose dependent manner in vitro , while homogenate co-treated with 17β-estradiol showed a significant reduction in lipid peroxidation. 17β-estradiol was also shown to be protective against Quinolinic Acid in vivo . These results could explain the neuroprotective effect of 17β-estradiol.
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17Beta-estradiol protects against Quinolinic Acid-induced lipid peroxidation in the rat brain.
Metabolic brain disease, 2000Co-Authors: Paula Heron, Santy DayaAbstract:The neurotoxin Quinolinic Acid has been identified as a causative agent in Huntington's disease and is a metabolite of the tryptophan pathway in the brain. In the present study, the in vivo and in vitro effect of 17β-estradiol on lipid peroxidation induced by Quinolinic Acid was investigated. For the in vivo experiments ovariectomized female rats were administered with 100 μg 17β-estradiol daily for seven days prior to and seven days following the intrahippocampal injection of 1 μmol Quinolinic Acid. The level of lipid peroxidation in brain homogenate was investigated using the thiobarbituric Acid test. The in vitro experiments were performed in brain homogenates of ovariectomized female rats. The homogenate was treated with Quinolinic Acid alone or in combination with 17β-estradiol. Quinolinic Acid increased lipid peroxidation in a dose dependent manner in vitro, while homogenate co-treated with 17β-estradiol showed a significant reduction in lipid peroxidation. 17β-estradiol was also shown to be protective against Quinolinic Acid in vivo. These results could explain the neuroprotective effect of 17β-estradiol.
Robert Schwarcz - One of the best experts on this subject based on the ideXlab platform.
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Immunohistochemical localization of Quinolinic Acid phosphoribosyltransferase in the human neostriatum.
Neuroscience, 1991Co-Authors: Etsuo Okuno, William O. Whetsell, Christer Köhler, Robert SchwarczAbstract:Abstract The localization and distribution of Quinolinic Acid phosphoribosyltransferase, the degradative enzyme of the endogenous excitotoxin Quinolinic Acid, were studied in the post mortem human neostriatum by immunohistochemistry. In eight neurologically normal human brains, Quinolinic Acid phosphoribosyl-transferase immunoreactivity was detected in both glial cells and neurons. Typically, glial cells containing Quinolinic Acid phosphoribosyltransferase immunoreactivity had numerous processes radiating from the cell bodies. In Nissl-counterstained sections, most Quinolinic Acid phosphoribosyltransferase-immuno-reactive glial cells showed round, large and pale nuclei. These morphological features indicate that they are probably astrocytes. Neurons containing Quinolinic Acid phosphoribosyltransferase immunoreactivity had different sizes and shapes and were tentatively classified into three subpopulations. Most were medium-sized cells with ovoid or elongated perikarya. Small Quinolinic Acid phosphoribosyltransferase-immunoreactive neurons, often spheroid in shape, were particularly noted in a zone of the caudate nucleus adjacent to the lateral ventricle. A few large Quinolinic Acid phosphoribosyltransferase-positive neurons were also present in both the caudate and putamen. The somatic and dendritic morphology of Quinolinic Acid phosphoribosyltransferase-immunoreactive neurons closely resembles that of aspiny neurons seen in Golgi preparations. The localization of the specific Quinolinic Acid-catabolizing enzyme in distinct populations of neostriatal cells suggests specific functional correlates. It remains to be examined how the anatomical organization of Quinolinic Acid phosphoribosyltransferase immunoreactivity relates to the degradation of Quinolinic Acid in the striatum, and if the morphological characteristics and distribution of Quinolinic Acid phospho-ribosyltransferase-immunoreactive cells are of relevance for the pathogenesis of neurodegenerative basal ganglia disorders.
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Quinolinic Acid catabolism is increased in cerebellum of patients with dominantly inherited olivopontocerebellar atrophy.
Annals of neurology, 1991Co-Authors: Stephen J. Kish, Deborah A. Parks, Yves Robitaille, Melvyn J. Ball, Lawrence J. Schut, Oleh Hornykiewicz, Robert SchwarczAbstract:We measured the activities of the enzymes responsible for the metabolism of the excitotoxin Quinolinic Acid, 3-hydroxyanthranilate oxygenase and Quinolinic Acid phosphoribosyltransferase, in autopsied brain of 11 patients with olivopontocerebellar atrophy. In cerebellar cortex, severe Purkinje cell loss was evident but with relative preservation of granule cells. As compared with the control subjects (n = 14), mean activity of 3-hydroxyanthranilate oxygenase was normal in cerebellar cortex from the patients with olivopontocerebellar atrophy, whereas Quinolinic Acid phosphoribosyltransferase activity was markedly increased (+92%, p less than 0.02). No significant changes in enzyme activities were found in samples from occipital cortex. Increased Quinolinic Acid phosphoribosyltransferase activity may represent a mechanism, in the degenerating cerebellum, to protect Quinolinic Acid-sensitive granule cells in patients with olivopontocerebellar atrophy.
