(1<i>R</i>,3<i>S</i>)‐1‐Aminocyclopentane‐1,3‐dicarboxylic acid (RS‐ACPD) reduces intracellular glutamate levels in astrocytes

Ye, Zu Cheng; Ransom, Bruce R.; Sontheimer, Harald

doi:10.1046/j.1471-4159.2001.00581.x

Cited by 13 publications

(8 citation statements)

References 63 publications

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“…Previous studies have showed that a significant increase in Glx was found in oligodendrogliomas and was used to discriminate them relative to low-grade astrocytomas (34). The increase in Glu that was observed in the Grade 3 glioma considered in our study is consistent with the observation that glioma cells may secrete Glu, resulting in an increase in extracellular Glu (35,36). Increased Glu could be also associated with inflammation in the peritumor tissues since activated microglia and brain macrophages express high affinity glutamate transporters (37) and stimulates tumor cell proliferation.…”

Section: Discussionsupporting

confidence: 92%

Comparison of T₁ and T₂ metabolite relaxation times in glioma and normal brain at 3T

Srinivasan

Ratiney

et al. 2008

Magnetic Resonance Imaging

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Purpose: To measure T 1 and T 2 relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. Materials and Methods:A total of 23 patients with gliomas and 10 volunteers were studied with single-voxel two-dimensional (2D) J-resolved point-resolved spectral selection (PRESS) using a 3T MR scanner. Voxels were chosen in normal appearing white matter (WM) and in regions of tumor. The T 1 and T 2 of choline containing compounds (Cho), creatine (Cr), and N-acetyl aspartate (NAA) were estimated.Results: Metabolite T 1 relaxation values in gliomas were not significantly different from values in normal WM. The T 2 of Cho and Cr were statistically significantly longer for grade 4 gliomas than for normal WM but the T 2 of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P Ͻ 0.001). Conclusion:The differential increase in T 2 for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/ NAA are higher in tumor at longer echo times (TEs) relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MR spectroscopic imaging (MRSI) data, in which limited time is available and only one TE can be used. GLIOMAS ACCOUNT FOR THE MAJORITY of primary brain tumors and vary from benign to malignant. Among all the gliomas, glioblastoma multiforme (GBM) is both the most common and the most malignant, with a relatively poor prognosis. Proton magnetic resonance spectroscopy ( 1 H-MRS) is a powerful noninvasive tool that has been used for the assessment of metabolites in gliomas and the biochemical profiles of brain tumors have been widely studied (1-4). A general marker of brain tumors is the elevation of choline-containing compounds (Cho), which is thought to be due to increased cell density and membrane turnover in neoplasms, and the reduction of the neural marker Nacetyl aspartate (NAA). The availability of higher field strength MR scanners and multichannel radio frequency coils offer the potential of higher signal-to-noise ratio (SNR) and better spectral resolution (5) that can be used to either shorten acquisition time, decrease spatial resolution, or improve detection of other brain metabolites; such as, glutamate (Glu), a main excitatory neurotransmitter; glutamine (Gln), which acts as a detoxifier; and myo-inositol (mI), which is predominantly located within astrocytes.In planning the data acquisition parameters for using MR spectroscopic imaging (MRSI) to determine the spatial extent of tumor vs. normal brain tissue, it is important to consider how to select values that will emphasize the contrast between metabolites in the different regions. Because of the restrictions on clinical scan time, the repetition time (TR) for acquiring MRSI data is often set at one to two seconds and it is usually only possible to acq...

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Section: Discussionsupporting

confidence: 92%

Comparison of T₁ and T₂ metabolite relaxation times in glioma and normal brain at 3T

Srinivasan

Ratiney

et al. 2008

Magnetic Resonance Imaging

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“…High glucose may or may not influence experimental outcome, but diabetic complications are, nevertheless, a concern for astrocytes and neurons grown in high glucose, and it is important to re-evaluate the results of such studies (e.g. 20 mmol/l glucose: Ye et al, 2001, 2003, 2009; McCoy and Sontheimer, 2010; 25 mmol/l glucose: Sorg and Magistretti, 1991; Yu et al., 1993; Takahashi et al, 1995; Itoh et al, 2003; Pellerin and Magistretti, 2005, 1994; Chenal and Pellerin, 2007; and 50 mmol/l glucose: Bliss et al, 2004). Also, Methods sections in published studies sometimes only identify the ‘generic’ culture medium (e.g.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycaemia and Diabetes Impair Gap Junctional Communication among Astrocytes

et al. 2010

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Sensory and cognitive impairments have been documented in diabetic humans and animals, but the pathophysiology of diabetes in the central nervous system is poorly understood. Because a high glucose level disrupts gap junctional communication in various cell types and astrocytes are extensively coupled by gap junctions to form large syncytia, the influence of experimental diabetes on gap junction channel-mediated dye transfer was assessed in astrocytes in tissue culture and in brain slices from diabetic rats. Astrocytes grown in 15–25 mmol/l glucose had a slow-onset, poorly reversible decrement in gap junctional communication compared with those grown in 5.5 mmol/l glucose. Astrocytes in brain slices from adult STZ (streptozotocin)-treated rats at 20–24 weeks after the onset of diabetes also exhibited reduced dye transfer. In cultured astrocytes grown in high glucose, increased oxidative stress preceded the decrement in dye transfer by several days, and gap junctional impairment was prevented, but not rescued, after its manifestation by compounds that can block or reduce oxidative stress. In sharp contrast with these findings, chaperone molecules known to facilitate protein folding could prevent and rescue gap junctional impairment, even in the presence of elevated glucose level and oxidative stress. Immunostaining of Cx (connexin) 43 and 30, but not Cx26, was altered by growth in high glucose. Disruption of astrocytic trafficking of metabolites and signalling molecules may alter interactions among astrocytes, neurons and endothelial cells and contribute to changes in brain function in diabetes. Involvement of the microvasculature may contribute to diabetic complications in the brain, the cardiovascular system and other organs.

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“…Multiple amino acid concentrations (Arg, Asn, Asp, Gln, Glu, Gly, Ser, Tau, Thr) in the lyophilized heart extracts dissolved in 2 H2O were determined by HPLC. Amino acids were precolumn derivatized with o-phthalialdehyde (Sigma, St. Louis, MO), separated, and measured as previously described (38).…”

Section: Methodsmentioning

confidence: 99%

Thyroid hormone controls myocardial substrate metabolism through nuclear receptor-mediated and rapid posttranscriptional mechanisms

Hyyti

Xue

Buroker

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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Thyroid hormone regulates metabolism through transcriptional and posttranscriptional mechanisms. The integration of these mechanisms in heart is poorly understood. Therefore, we investigated control of substrate flux into the citric acid cycle (CAC) by thyroid hormone using retrogradely perfused isolated hearts (n = 20) from control (C) and age-matched thyroidectomized rats (T). We determined substrate flux and fractional contributions (Fc) to the CAC by 13C-NMR spectroscopy and isotopomer analyses in hearts perfused with [1,3-(13)C]acetoacetic acid (0.17 mM), L-[3-(13)C]lactic acid (LAC, 1.2 mM), [U-13C]long-chain mixed free fatty acids (FFA, 0.35 mM), and unlabeled glucose. Some T hearts were supplied triiodothyronine (T3, 10 nM; TT) for 60 min. Prolonged hypothyroid state reduced myocardial oxygen consumption, although T3 produced no significant change. Hypothyroidism reduced overall CAC(flux) but selectively altered only FFA(flux) among the individual substrates, though LAC(flux) trended upward. T3 rapidly decreased lactate Fc and flux. 13C labeling of glutamine through glutamate was increased in T with further enhancement in TT. The glutamate-to-glutamine ratio was significantly lower in T and TT. Immunoblots detected a decrease in hypothyroid hearts for muscle carnitine palmitoyltransferase I (CPT I) and a marked increase in pyruvate dehydrogenase kinase (PDK)-2 with no changes in liver CPT I, PDK-4, or hexokinase 2. TT, but not T, displayed elevated glutamine synthetase (GS) expression. These studies showed that T3 regulates cardiac metabolism through integration of several mechanisms, including changes in oxidative enzyme content and rapid modulation of individual substrates fluxes. T3 also moderates forward glutamine flux, possibly by increasing the overall activity of GS.

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(1R,3S)‐1‐Aminocyclopentane‐1,3‐dicarboxylic acid (RS‐ACPD) reduces intracellular glutamate levels in astrocytes

Cited by 13 publications

References 63 publications

Comparison of T₁ and T₂ metabolite relaxation times in glioma and normal brain at 3T

Comparison of T₁ and T₂ metabolite relaxation times in glioma and normal brain at 3T

Hyperglycaemia and Diabetes Impair Gap Junctional Communication among Astrocytes

Thyroid hormone controls myocardial substrate metabolism through nuclear receptor-mediated and rapid posttranscriptional mechanisms

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(1R,3S)‐1‐Aminocyclopentane‐1,3‐dicarboxylic acid (RS‐ACPD) reduces intracellular glutamate levels in astrocytes

Cited by 13 publications

References 63 publications

Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3T

Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3T

Hyperglycaemia and Diabetes Impair Gap Junctional Communication among Astrocytes

Thyroid hormone controls myocardial substrate metabolism through nuclear receptor-mediated and rapid posttranscriptional mechanisms

Contact Info

Product

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Comparison of T₁ and T₂ metabolite relaxation times in glioma and normal brain at 3T

Comparison of T₁ and T₂ metabolite relaxation times in glioma and normal brain at 3T