The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
Jun Shen - One of the best experts on this subject based on the ideXlab platform.
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Modeling the Glutamate–glutamine Neurotransmitter cycle
Frontiers in Neuroenergetics, 2013Co-Authors: Jun ShenAbstract:Glutamate is the principal excitatory Neurotransmitter in brain. Although it is rapidly synthesized from glucose in neural tissues the biochemical processes for replenishing the Neurotransmitter Glutamate after Glutamate release involve the Glutamate-glutamine cycle. Numerous in vivo 13C magnetic resonance spectroscopy experiments since 1994 by different laboratories have consistently concluded: i) the Glutamate-glutamine cycle is a major metabolic pathway with a flux rate substantially greater than those suggested by early studies of cell cultures and brain slices; ii) the Glutamate-glutamine cycle is coupled to a large portion of the total energy demand of brain function. The dual roles of Glutamate as the principal Neurotransmitter in the CNS and as a key metabolite linking carbon and nitrogen metabolism make it possible to probe Glutamate Neurotransmitter cycling using magnetic resonance spectroscopy by measuring the labeling kinetics of Glutamate and glutamine. At the same time, comparing to non-amino acid Neurotransmitters, the added complexity makes it more challenging to quantitatively separate neurotransmission events from metabolism. Over the past few years our understanding of the neuronal-astroglial two compartment metabolic model of the Glutamate-glutamine cycle has been greatly advanced. In particular, the importance of isotopic dilution of glutamine in determining the Glutamate-glutamine cycling rate using [1-13C] or [1,6-13C2]glucose has been demonstrated and reproduced by different laboratories. In this article, recent developments in the two-compartment modeling of the Glutamate-glutamine cycle are reviewed. In particular, the effects of isotopic dilution of glutamine on various labeling strategies for determining the Glutamate-glutamine cycling rate are analyzed. Experimental strategies for measuring the Glutamate-glutamine cycling flux that are insensitive to isotopic dilution of glutamine are also suggested.
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modeling the Glutamate glutamine Neurotransmitter cycle
Frontiers in Neuroenergetics, 2013Co-Authors: Jun ShenAbstract:Glutamate is the principal excitatory Neurotransmitter in brain. Although it is rapidly synthesized from glucose in neural tissues the biochemical processes for replenishing the Neurotransmitter Glutamate after Glutamate release involve the Glutamate-glutamine cycle. Numerous in vivo 13C magnetic resonance spectroscopy experiments since 1994 by different laboratories have consistently concluded: i) the Glutamate-glutamine cycle is a major metabolic pathway with a flux rate substantially greater than those suggested by early studies of cell cultures and brain slices; ii) the Glutamate-glutamine cycle is coupled to a large portion of the total energy demand of brain function. The dual roles of Glutamate as the principal Neurotransmitter in the CNS and as a key metabolite linking carbon and nitrogen metabolism make it possible to probe Glutamate Neurotransmitter cycling using magnetic resonance spectroscopy by measuring the labeling kinetics of Glutamate and glutamine. At the same time, comparing to non-amino acid Neurotransmitters, the added complexity makes it more challenging to quantitatively separate neurotransmission events from metabolism. Over the past few years our understanding of the neuronal-astroglial two compartment metabolic model of the Glutamate-glutamine cycle has been greatly advanced. In particular, the importance of isotopic dilution of glutamine in determining the Glutamate-glutamine cycling rate using [1-13C] or [1,6-13C2]glucose has been demonstrated and reproduced by different laboratories. In this article, recent developments in the two-compartment modeling of the Glutamate-glutamine cycle are reviewed. In particular, the effects of isotopic dilution of glutamine on various labeling strategies for determining the Glutamate-glutamine cycling rate are analyzed. Experimental strategies for measuring the Glutamate-glutamine cycling flux that are insensitive to isotopic dilution of glutamine are also suggested.
Caroline Anderson - One of the best experts on this subject based on the ideXlab platform.
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Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment
Journal of NeuroVirology, 2014Co-Authors: Ned Sacktor, Sachiko Miyahara, Giovanni Schifitto, Norman J. Haughey, Julia L. Drewes, M. Christine Zink, Scott Evans, Bruce Cohen, David Graham, Caroline AndersonAbstract:Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased Neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, “Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment,” minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, Neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), Glutamate, Neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers. These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.
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Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.
Journal of NeuroVirology, 2014Co-Authors: Ned Sacktor, Sachiko Miyahara, Scott R. Evans, Giovanni Schifitto, Bruce Arnold Cohen, Norman J. Haughey, Julia L. Drewes, David R. Graham, M. Christine Zink, Caroline AndersonAbstract:Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased Neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, “Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment,” minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, Neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), Glutamate, Neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.
Yasuyuki Fukumaki - One of the best experts on this subject based on the ideXlab platform.
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Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed across the gene region.
American Journal of Medical Genetics, 2020Co-Authors: Chieko Makino, Hiroki Shibata, Hideaki Ninomiya, Yo Fujii, Rumiko Kikuta, Naotsugu Hirata, Ayako Tani, Atsushi Shibata, Nobutada Tashiro, Yasuyuki FukumakiAbstract:The Glutamatergic dysfunction hypothesis suggests that genes involved in the Glutamate Neurotransmitter system are candidates for schizophrenia-susceptibility genes. We have been conducting systematic studies of the association between Glutamate receptors and schizophrenia. We report on a positive association of some haplotypes of the AMPA receptor subunit GluR4 gene (GRIA4) with schizophrenia. We genotyped 100 Japanese schizophrenics and 100 controls for six single nucleotide polymorphism (SNP) markers distributed at intervals of about 50 kb in the GRIA4 region, and estimated the degree of linkage disequilibrium (LD) between the SNPs. We constructed haplotypes of the SNPs in LD using the EM algorithm to test their association with schizophrenia. Significant associations were detected for the combination of SNP4-5 (χ2 = 12.54, df = 3, P = 0.0057, P = 0.029 with Bonferroni correction) and for the combination of SNP3-4-5 (χ2 = 18.9, df = 7, P = 0.0085, P = 0.043 with Bonferroni correction). These results suggest that at least one susceptibility locus for schizophrenia is located within or very close to the GRIA4 region in Japanese. © 2003 Wiley-Liss, Inc.
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Association analysis of the glutamic acid decarboxylase 2 and the glutamine synthetase genes (GAD2, GLUL) with schizophrenia
Psychiatric Genetics, 2009Co-Authors: Shinsaku Arai, Hiroki Shibata, Mayumi Sakai, Hideaki Ninomiya, Nakao Iwata, Norio Ozaki, Yasuyuki FukumakiAbstract:ObjectiveAs dysfunction of Glutamatergic neurotransmission is one of the plausible hypotheses for the pathogenesis of schizophrenia, genes involved in the Glutamate Neurotransmitter system are candidates for schizophrenia susceptibility. The aim of this study is to clarify the contribution of two ge
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Glutamate receptor genes as candidates for schizophrenia susceptibility
Drug Development Research, 2003Co-Authors: Yasuyuki Fukumaki, Hiroki ShibataAbstract:The Glutamatergic dysfunction hypothesis suggests that genes involved in the Glutamate Neurotransmitter system are candidates for schizophrenia-susceptibility genes. We have been doing systematic studies of the association of schizophrenia with each member of the Glutamate receptor gene family. In this review, we summarize our results of association studies of five Glutamate receptor genes, two of which are metabotropic, GRM2 and GRM3, whereas the other four are ionotropic, GRIA4, GRIK1, GRIK2 and GRIN1. Haplotype analyses using combinations of SNPs evenly distributed across the relevant genes showed significant associations of GRM3 and GRIA4 with schizophrenia. We discuss the possible involvement of Glutamate receptor genes in the pathogenesis of schizophrenia, on the basis of association as well as linkage and postmortem studies previously reported. Replication of positive associations using different populations and the family-based study are necessary to confirm the results. Generation of gene-manipulated mice to represent endophenotypes of schizophrenia would be an alternative way to verify susceptibility genes. Some members of the Glutamate receptor family may be promising targets for schizophrenia drugs. Drug Dev. Res. 60:137–151, 2003. © 2003 Wiley-Liss, Inc.
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Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed across the gene region.
American journal of medical genetics. Part B Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics, 2003Co-Authors: Chieko Makino, Hiroki Shibata, Hideaki Ninomiya, Yo Fujii, Rumiko Kikuta, Naotsugu Hirata, Ayako Tani, Atsushi Shibata, Nobutada Tashiro, Yasuyuki FukumakiAbstract:The Glutamatergic dysfunction hypothesis suggests that genes involved in the Glutamate Neurotransmitter system are candidates for schizophrenia-susceptibility genes. We have been conducting systematic studies of the association between Glutamate receptors and schizophrenia. We report on a positive association of some haplotypes of the AMPA receptor subunit GluR4 gene (GRIA4) with schizophrenia. We genotyped 100 Japanese schizophrenics and 100 controls for six single nucleotide polymorphism (SNP) markers distributed at intervals of about 50 kb in the GRIA4 region, and estimated the degree of linkage disequilibrium (LD) between the SNPs. We constructed haplotypes of the SNPs in LD using the EM algorithm to test their association with schizophrenia. Significant associations were detected for the combination of SNP4-5 (chi(2) = 12.54, df = 3, P = 0.0057, P = 0.029 with Bonferroni correction) and for the combination of SNP3-4-5 (chi(2) = 18.9, df = 7, P = 0.0085, P = 0.043 with Bonferroni correction). These results suggest that at least one susceptibility locus for schizophrenia is located within or very close to the GRIA4 region in Japanese.
Ned Sacktor - One of the best experts on this subject based on the ideXlab platform.
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Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment
Journal of NeuroVirology, 2014Co-Authors: Ned Sacktor, Sachiko Miyahara, Giovanni Schifitto, Norman J. Haughey, Julia L. Drewes, M. Christine Zink, Scott Evans, Bruce Cohen, David Graham, Caroline AndersonAbstract:Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased Neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, “Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment,” minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, Neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), Glutamate, Neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers. These results suggest that minocycline may decrease lipid markers of oxidative stress (ceramides) in individuals with HAND; however, an effect of minocycline on other CSF markers was not observed. A larger sample size is needed to further validate these results.
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Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment.
Journal of NeuroVirology, 2014Co-Authors: Ned Sacktor, Sachiko Miyahara, Scott R. Evans, Giovanni Schifitto, Bruce Arnold Cohen, Norman J. Haughey, Julia L. Drewes, David R. Graham, M. Christine Zink, Caroline AndersonAbstract:Elevated cerebrospinal fluid (CSF) levels of markers of oxidative stress, neuronal injury, and inflammation and decreased Neurotransmitter levels have been reported in HIV-associated neurocognitive disorders (HAND). Minocycline may have a neuroprotective effect by inhibiting inducible nitric oxide synthase, which produces nitric oxide, a compound that induces oxygen free radical production. In A5235, “Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment,” minocycline was not associated with cognitive improvement, but the effect on the above CSF measures was not examined previously. The objective of this study was to examine the effect of minocycline on markers of oxidative stress, neuronal injury, Neurotransmitter levels, and inflammation from CSF in participants in A5235. One hundred seven HIV+ individuals received either minocycline 100 mg or placebo orally every 12 h for 24 weeks. Twenty-one HIV+ individuals received the optional lumbar punctures. Lipid and protein markers of oxidative stress (e.g., ceramides and protein carbonyls), Glutamate, Neurotransmitter precursors, kynurenine metabolites, neurofilament heavy chain, and inflammatory cytokines were measured in the CSF before and after treatment. The 24-week change in ceramides was larger in a beneficial direction in the minocycline group compared to the placebo group. The two groups did not differ in the 24-week changes for other markers.
Alvin Zipursky - One of the best experts on this subject based on the ideXlab platform.
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The Developing Nervous System: A Series of Review Articles: Neurobiology of Hypoxic-Ischemic Injury in the Developing Brain
Pediatric Research, 2001Co-Authors: Michael V Johnston, William H Trescher, Akira Ishida, Wako Nakajima, Alvin ZipurskyAbstract:Hypoxic ischemia is a common cause of damage to the fetal and neonatal brain. Although systemic and cerebrovascular physiologic factors play an important role in the initial phases of hypoxic-ischemic injuries, the intrinsic vulnerability of specific cell types and systems in the developing brain may be more important in determining the final pattern of damage and functional disability. Excitotoxicity, a term applied to the death of neurons and certain other cells caused by overstimulation of excitatory, mainly Glutamate, Neurotransmitter receptors, plays a critical role in these processes. Selected neuronal circuits as well as certain populations of glia such as immature periventricular oligodendroglia may die from excitotoxicity triggered by hypoxic ischemia. These patterns of neuropathologic vulnerability are associated with clinical syndromes of neurologic disability such as the extrapyramidal and spastic diplegia forms of cerebral palsy. The cascade of biochemical and histopathologic events triggered by hypoxic ischemia can extend for days to weeks after the insult is triggered, creating the potential for therapeutic interventions.
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Neurobiology of hypoxic-ischemic injury in the developing brain.
Pediatric Research, 2001Co-Authors: Michael V Johnston, William H Trescher, Akira Ishida, Wako Nakajima, Alvin ZipurskyAbstract:Hypoxic ischemia is a common cause of damage to the fetal and neonatal brain. Although systemic and cerebrovascular physiologic factors play an important role in the initial phases of hypoxic-ischemic injuries, the intrinsic vulnerability of specific cell types and systems in the developing brain may be more important in determining the final pattern of damage and functional disability. Excitotoxicity, a term applied to the death of neurons and certain other cells caused by overstimulation of excitatory, mainly Glutamate, Neurotransmitter receptors, plays a critical role in these processes. Selected neuronal circuits as well as certain populations of glia such as immature periventricular oligodendroglia may die from excitotoxicity triggered by hypoxic ischemia. These patterns of neuropathologic vulnerability are associated with clinical syndromes of neurologic disability such as the extrapyramidal and spastic diplegia forms of cerebral palsy. The cascade of biochemical and histopathologic events triggered by hypoxic ischemia can extend for days to weeks after the insult is triggered, creating the potential for therapeutic interventions.