Eunjung Bang

In vivo and ex vivo evidence for ketamine-induced hyperglutamatergic activity in the cerebral cortex of the rat: Potential relevance to schizophrenia.

Subanesthetic doses of ketamine, a noncompetitive N‐methyl‐D‐aspartate (NMDA) receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in patients with schizophrenia. In the present study, in vivo 1H‐MRS and ex vivo 1H high‐resolution magic angle spinning (HR‐MAS) spectroscopy was used to examine the brain metabolism of rats treated with subanesthetic doses of ketamine (30 mg/kg) for 6 days. A single voxel localization sequence (PRESS, TR/TE = 4000/20 ms and NEX = 512) was used to acquire the spectra in a 30‐µl voxel positioned in the cerebral cortex (including mainly PFC) of the rats (ketamine group: n = 12; saline group: n = 12) anesthetized with isoflurane. After the in vivo 1H‐MRS acquisition, the animals were sacrificed and the cerebral cortex tissues were extracted (ketamine group: n = 7; saline group: n = 7) for ex vivo 1H HR‐MAS spectroscopy (CPMG sequence, 2.0‐s presaturation delay, 2.0‐s acquisition time, 128 transients and 4‐ms inter‐pulse delay) using a 500‐MHz NMR spectrometer. All proton metabolites were quantified using the LCModel. For the in vivo spectra, there was a significant increase in glutamate concentration in the cerebral cortex of the ketamine group compared with the controls (p < 0.05). For the ex vivo HR‐MAS spectra, there was a significant increase in the glutamate/total creatine ratio, and a decrease in the glutamine/total creatine and glutamine/glutamate ratios in the cerebral cortex tissue of the ketamine group compared with the controls. The results of the present study demonstrated that administration of subanesthetic doses of ketamine in the rat may exert at least part of their effect in the cerebral cortex by activation of glutamatergic neurotransmission. Copyright

Identification of N-ethyl-α-ethylphenethylamine in crystalline powder seized for suspected drug trafficking: a research chemical or a new designer drug?

A crystalline powder was found in an unclaimed lost article shipped from Vietnam to South Korea, and it was seized by narcotics agents as an item of suspicious trade. The chemical was suspected to be methamphetamine crystals, and was sent to the National Forensic Service for forensic identification. Elucidation of the chemical structure was carried out using gas chromatography–electron impact ionization–mass spectrometry, liquid chromatography–time-of-flight–mass spectrometry, and 1D and 2D nuclear magnetic resonance spectroscopy. The compound was identified as N-ethyl-α-ethylphenethylamine. Although the narcotic effect of this compound remains unverified, it may be classified as a phenethylamine-based designer drug on the basis of its structure. It appeared that the recipient of this article sought to abuse this chemical in the same way as amphetamines. There is a possibility that this chemical will be widely abused for recreational use in the near future.

Chronic repetitive transcranial magnetic stimulation enhances GABAergic and cholinergic metabolism in chronic unpredictable mild stress rat model: 1H-NMR spectroscopy study at 11.7T

Gamma-animobutyric acid (GABA) systems are emerging as targets for development of medications for mood disorders. Deficits in GABA-containing neurons are consistently reported in psychiatric disease, particularly in the prefrontal cortex and hippocampus. Repetitive transcranial magnetic stimulation (rTMS) that use magnetic field to stimulate focal cortical regions with electrical current have a potential therapeutic effects with non-invasive and painless method. In this study, we used chronic unpredictable mild stress (CUMS) rat model of depression to investigate the behavioral and neurochemical alterations. Furthermore, chronic rTMS treatment effect on neurochemical profile in prefrontal cortex and hippocampus of rats were assessed. The CUMS induced significant reductions in absolute sucrose intake and sucrose preference. In addition, high-resolution (1)H-NMR spectra from brain extracts revealed significantly reduced prefrontal and hippocampal GABA levels in CUMS rats compared to control. The behavioral and neurochemical changes were reversed by chronic rTMS treatment. Furthermore, chronic rTMS treatments results in differential effects on different brain regions. Our results suggest specific and regionally different metabolic response to chronic rTMS treatment in animal model of depression.

A 1H HR-MAS NMR-Based Metabolomic Study for Metabolic Characterization of Rice Grain from Various Oryza sativa L. Cultivars

Rice grain metabolites are important for better understanding of the plant physiology of various rice cultivars and thus for developing rice cultivars aimed at providing diverse processed products. However, the variation of global metabolites in rice grains has rarely been explored. Here, we report the identification of intra- or intercellular metabolites in rice (Oryza sativa L.) grain powder using a (1)H high-resolution magic angle spinning (HR-MAS) NMR-based metabolomic approach. Compared with nonwaxy rice cultivars, marked accumulation of lipid metabolites such as fatty acids, phospholipids, and glycerophosphocholine in the grains of waxy rice cultivars demonstrated the distinct metabolic regulation and adaptation of each cultivar for effective growth during future germination, which may be reflected by high levels of glutamate, aspartate, asparagine, alanine, and sucrose. Therefore, this study provides important insights into the metabolic variations of diverse rice cultivars and their associations with environmental conditions and genetic backgrounds, with the aim of facilitating efficient development and the improvement of rice grain quality through inbreeding with genetic or chemical modification and mutation.

Investigation of relative metabolic changes in the organs and plasma of rats exposed to X-ray radiation using HR-MAS (1)H NMR and solution (1)H NMR.

Excess exposure to ionizing radiation generates reactive oxygen species and increases the cellular inflammatory response by modifying various metabolic pathways. However, an investigation of metabolic perturbations and organ‐specific responses based on the amount of radiation during the acute phase has not been conducted. In this study, high‐resolution magic‐angle‐spinning (HR‐MAS) NMR and solution NMR‐based metabolic profiling were used to investigate dose‐dependent metabolic changes in multiple organs and tissues – including the jejunum, spleen, liver, and plasma – of rats exposed to X‐ray radiation. The organs, tissues, and blood samples were obtained 24, 48, and 72 h after exposure to low‐dose (2 Gy) and high‐dose (6 Gy) X‐ray radiation and subjected to metabolite profiling and multivariate analyses. The results showed the time course of the metabolic responses, and many significant changes were detected in the high‐dose compared with the low‐dose group. Metabolites with antioxidant properties showed acute responses in the jejunum and spleen after radiation exposure. The levels of metabolites related to lipid and protein metabolism were decreased in the jejunum. In addition, amino acid levels increased consistently at all post‐irradiation time points as a consequence of activated protein breakdown. Consistent with these changes, plasma levels of tricarboxylic acid cycle intermediate metabolites decreased. The liver did not appear to undergo remarkable metabolic changes after radiation exposure. These results may provide insight into the major metabolic perturbations and mechanisms of the biological systems in response to pathophysiological damage caused by X‐ray radiation. Copyright

Metabotyping of rice (Oryza sativa L.) for understanding its intrinsic physiology and potential eating quality

Rice (Oryza sativa L.), the major staple food in many countries, has genetic diversity adapted to different environmental conditions. However, metabolic traits about diverse rice plants are rarely discovered. In the present study, rice leaves and grains were collected at whole growth stages from late (LMC) and early (EMC) maturing cultivars. Metabolic dependences of rice plants on both growth and cultivar were investigated in their leaves and grains through NMR-based metabolomics approach. Rice leaf metabolome were differently regulated between two rice cultivars, thereby affecting variations of rice grain metabolome. Sucrose levels in leaves of EMC were markedly decreased compared to those in LMC, and more accumulations of sucrose, amino acids and free fatty acids were found in grains of EMC. These distinct metabolisms between EMC and LMC rice cultivars were associated with temperature during their growing seasons and might affect the eating quality of rice. The current study highlights that metabolomic approach of rice leaves and grains could lead to better understanding of the relationship between their distinct metabolisms and environmental conditions, and provide novel insights to metabolic qualities of rice grains.

Metabolic Alterations of the Zebrafish Brain after Acute Alcohol Treatment by 1 H Nuclear Magnetic Resonance Spectroscopy

The purpose of this study is to investigate the metabolic alterations associated with acute alcohol treatment in zebrafish by 1H nuclear magnetic resonance spectroscopy (NMRS). The brain metabolism of zebrafish was investigated after acute alcohol treatment (one-hour long exposure of adult fish to 0.00%, 0.25%, 0.50%, or 1.00% ethyl alcohol) with whole brain extraction. The results of this study showed that glutamate (Glu) was significantly decreased, scyllo-inositol (sIns) showed a small apparent increase only in the highest acute treatment dose group, and myoinositol (mIns) showed a significant decrease. [Glu]/[tCr] and [mIns]/[tCr] levels were significantly reduced regardless of the alcohol dose, and [sIns]/[tCr] was increased in the highest alcohol treatment dose group. The present NMR study revealed that specific metabolites, such as Glu and mIns, were substantially decreased in case of acute alcohol exposed zebrafish brain.

Analysis of in vitro 2D-COSY on Human Brain Metabolites for Molecular Stereochemistry

To investigate the 3-bond connectivity of human brain metabolites by scalar coupling interaction through 2D-correlation spectroscopy (COSY) techniques using high field NMR spectroscopy. All NMR experiments were performed at 298K on Unity Inova 500 or 600 (Varian Inc.) equipped with a triple resonance probe head with z-shield gradient. Human brain metabolites were prepared with 10% . Two dimensional 2D COSY spectra were acquired with 4096 complex data points in and 128 or 256 increments in dimension. The spectral width was 9615.4 Hz and solvent suppression was achieved using presaturation using low power irradiation of the water resonance during 2s of relaxation delay. NMR data were processed using VNMRJ (Varian Instrument) software and all the chemical shifts were referenced to the methyl resonance of N-acetyl aspartate (NAA) peak at 2.0 ppm. Total 10 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), lactate (Lac), taurine (Tau), -aminobutyricacid (GABA), alanine (Ala) were included for major target metabolites. Symmetrical 2D-COSY spectra were successfully acquired. Total 14 COSY cross peaks were observed even though there were parallel/orthogonal noisy peaks induced by water suppression. Except for Cr, all of human brain metabolites produced COSY cross peaks. The spectra of NAA methyl proton at 2.02 ppm and Glu methylene proton () at 2.11 ppm and Gln methylene proton () at 2.14 ppm were overlapped in the similar resonance frequency between 2.00 ppm and 2.15 ppm. The present study demonstrated that in vitro 2D-COSY represented the 3-bond connectivity of human brain metabolites by scalar coupling interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2D-COSY study. Also it would be helpful to determine the molecular stereochemistry in vivo by using two-dimensional MR spectroscopy