• The Korean Journal of Physiology and Pharmacology
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• v.1 no.2
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• pp.127-133
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• 1997

Lithium remains the most widely used therapeutic agent for bipolar affective disorder, particularly mania. Although many investigators have studied the effects of lithium on abnormalities in monoamine neuro-transmitter as a pathophysiological basis of affective disorder, the action mechanism of lithium ion remains still unknown. To explore the action mechanism of lithium in the brain, we examined the effects of lithium on the extrasynaptosomal concentrations of catecholamines and their metabolites. Synaptosomes were prepared from the rat forebrains and assays of catecholamines and metabolites were made using HPLC with an electrochemical detector. Lithium of 1mM decreased the extrasynaptosomal concentrations of NE from the control group of $3.07{\pm}1.19$ to the treated group of $0.00{\pm}0.00$ (ng/ml of synaptosomal suspension) but not that of DHPG. It can be suggested that lithium increases synaptosomal uptake of NE. Increased intraneuronal uptake of NE would decrease neurotransmission and extraneuronal metabolism of NE. Because increased brain NE metabolism and neurotransmission have been suggested as important components in the pathophysiology of bipolar affective disorder, especially mania, lithium-induced increase of intraneuronal NE uptake can be suspected as an action mechanism of therapeutic effect of lithium in manic patient, possibly in bipolar affective disorder.

• Journal of Nutrition and Health
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• v.27 no.2
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• pp.153-161
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• 1994

We fed high trypotophan diet(3.5% tryptophan/diet(w/w) to mice for 7 days and treated then with 3 hour immobilization(IMMB) stress to investigate tryptophan metabolism and immunomodulation. The levels of serum tryptophan, brain tryptophan, serotonin(5HT) and 5-hydroxyindoleacetic acid(5HIAA) in the tryptophan diet fed animals were higher than those of the normal diet fed animals. Feeding tryptophan supplemented diet to stressed animal significantly decreased the levels of serum and brain tryptophan and 5HT levels. However, the amount of 5HIAA which is the metabolite of serotonin was increased in brain. Plasma corticosterone level was increased by the stress in both groups but the degree of this increase was smaller in high tryptophan fed animals. The relative numbers of CD8+ T cells, CD4+ T cells and B cells in spleen were decreased in high tryptophan diet fed and stressed animals compared to control diet fed and no stressed animals. CD8+ T cells decreased more than CD4+ T cells. The decrease of CD8+ T cells in high tryptophan fed and stressed animals was similar to that in high tryptophan fed animals or normal diet fed and stressed animals. Stress and tryptophan supplement acted synergistically to decrease the number of B cells. This study suggests that stress and tryptophan supplement could modify the number of lymphocyte cells, and indicates that the interaction of stress and tryptophan supplement on immune fuction depends on the types of immune cells.

• Korean Journal of Radiology
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• v.23 no.3
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• pp.381-382
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• 2022

• Molecules and Cells
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• v.42 no.11
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• pp.739-746
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• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• Journal of Korean Neurosurgical Society
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• v.63 no.6
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• pp.689-697
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• 2020

Objective : Cerebral edema is the predominant mechanism of secondary inflammation after intracerebral hemorrhage (ICH). Pioglitazone, peroxisome proliferator-activated receptor gamma agonist has been shown to play a role in regulation of central nervous system inflammation. Here, we examined the pharmacological effects of pioglitazone in an ICH mouse model and investigated its regulation on NLRP3 inflammasome and glucose metabolism. Methods : The ICH model was established in C57 BL/6 mice by the stereotactical inoculation of blood (30 µL) into the right frontal lobe. The treatment group was administered i.p. pioglitazone (20 mg/kg) for 1, 3, and 6 days. The control group was administered i.p. phosphate-buffered saline for 1, 3, and 6 days. We investigated brain water contents, NLRP3 expression, and changes in the metabolites in the ICH model using liquid chromatography-tandem mass spectrometry. Results : On day 3, brain edema in the mice treated with pioglitazone was decreased more than that in the control group. Expression levels of NLRP3 in the ICH model treated with pioglitazone were decreased more than those of the control mice on days 3 and 7. The pioglitazone group showed higher levels of glycolytic metabolites than those in the ICH mice. Lactate production was increased in the ICH mice treated with pioglitazone. Conclusion : Our results demonstrated less brain swelling following ICH in mice treated with pioglitazone. Pioglitazone decreased NLRP3-related brain edema and increased anaerobic glycolysis, resulting in the production of lactate in the ICH mice model. NLRP3 might be a therapeutic target for ICH recovery.

• Journal of Nutrition and Health
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• v.17 no.3
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• pp.199-209
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• 1984

Pregnant rats were fed a pyridoxine deficient diet during the gestation and lactation. DEF I group received the deficient diet from delivery ; DEF II group, from the 15 th day of gestation. Body and brain weights, brain protein, DNA, RNA, plasma GOT and GPT, and catecholamines were measured. Effect of MAO inhibiting drug, pargyline, was determined. Brain protein, DNA, and RNA of offsprings of deficient groups were significantly lower than the control group, but RNA/ DNA, brain weight/DNA, and protein/DNA show that cell number were more affected than cell size by the pyridoxine deficiency during the 3rd week of gestation and lactation. Plasma GOT activities were more significantly different than plasma GPT between the control and deficient group. Brain norepinephrine of offsprings of deficient group were significantly lower than the control, but brain dopamine content was not significantly different from the control. At 2nd and 3rd week, norepinephrine was significantly depressed in deficient groups. Pargyline treatment affected a 1.2 fold increase in catecholamines in 3hr while the control had a 1.5 fold increase. Thus norepinephrine and dopamine synthesis was depressed in the deficient groups. Dopaminergic neurons may be less dependent on pyridoxine level than neurons from norepinephrine. Pyridoxine deficiency in maternal diet is not so critical to brain catecholamines of offspring except to the neonatal rats.

• BMB Reports
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• v.53 no.11
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• pp.551-564
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• 2020

Proper development of the nervous system is critical for its function, and deficits in neural development have been implicated in many brain disorders. A precise and predictable developmental schedule requires highly coordinated gene expression programs that orchestrate the dynamics of the developing brain. Especially, recent discoveries have been showing that various mRNA chemical modifications can affect RNA metabolism including decay, transport, splicing, and translation in cell type- and tissue-specific manner, leading to the emergence of the field of epitranscriptomics. Moreover, accumulating evidences showed that certain types of RNA modifications are predominantly found in the developing brain and their dysregulation disrupts not only the developmental processes, but also neuronal activities, suggesting that epitranscriptomic mechanisms play critical post-transcriptional regulatory roles in development of the brain and etiology of brain disorders. Here, we review recent advances in our understanding of molecular regulation on transcriptome plasticity by RNA modifications in neurodevelopment and how alterations in these RNA regulatory programs lead to human brain disorders.

• Journal of Nutrition and Health
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• v.23 no.2
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• pp.108-114
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• 1990

The concentrations of $\alpha$-tocopherol in the brain, liver, and serum were studied with and without saponification process between control and vitamin E supplemented rats. Young rats, 80-120g body weight, were fed control and vitamin E supplemented diets, ad libitum, for four weeks. $\alpha$-Tocopherol concentrations were determined by high pressure liquid chromatography. The $\alpha$-tocopherol concentration per wet weight base in the brain tissue was significantly lower than that in the liver. Vitamin E supplementation had no effect on brain $\alpha$-tocopherol levels in contrast to the significant increase in lover $\alpha$-tocopherol concentration with and without saponification is significantly greater in the brain than in the liver or serum. Further study is needed to clarify the nature of interaction or /and binding between $\alpha$-tocopherol and the complex membrane system in brain tissue. It can be speculated from this and other studies that the metabolism and the nature of interaction of $\alpha$-tocopherol with the complex membrane system in brain tissue rich in polyunsaturated fatty acids seems different from that in liver tissue or serum.

• BMB Reports
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• v.36 no.2
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• pp.154-158
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• 2003

Collagen is a family of proteins which consists of several genetically distinct molecular species and is intimately involved in tissue organization, function, differentiation and development. The purpose of this study was to investigate the concentration of different hydroxyproline (Hyp) fractions viz., total, free, peptide-bound, protein-bound, soluble- and insoluble-collagen hydroxyproline (Hyp) in various bovine tissues. Results showed that liver had the highest concentration of free Hyp followed by kidney, brain, spleen, lungs, muscle and heart. Liver also had the highest concentration of peptide-bound collagen Hyp followed by kidney, heart, spleen, lungs, brain and muscle. The concentration of protein-bound collagen Hyp was highest in the liver, followed by kidney, spleen, lungs, muscle, brain and heart. Total Hyp was highest in the liver, followed by kidney, spleen, brain, heart, muscle and lungs. Liver also had significantly high concentration of collagen as compared to other tissues examined (P<0.001). Spleen had the significantly higher concentration of soluble-collagen Hyp when compared to other tissues (P<0.001). This was followed by heart, muscle, lungs, brain, kidney and liver. Heart had the highest concentration of insoluble-collagen Hyp followed by lungs, kidney, liver, muscle, spleen and brain. The variation among the insoluble-collagen Hyp concentration of heart and muscle, spleen and brain was significant (P<0.001). We speculate that these differences could be due to the variation in turn over of rate of collagen metabolism in this species.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.1-5
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• 2008

Primary brain tumor accounts for 1.4% of entire cancer. For males between the ages of 15 and 34 years, central nervous system tumors account for the leading cause of cancer death. $^{18}F-FDG$ PET has been reported that it can provide important diagnostic information relating to tumor grading and differentiation from non- tumorous condition. In addition, the degree of FDG metabolism carries prognostic significance. By mapping the metabolic pattern of heterogeneous tumors, $^{18}F-FDG$ PET can aid in targeting for stereotactic biopsy by selecting the subregions within the tumor that are most hypermetabolic and potentially have the highest grade. According to clinical research data, FOG PET is expected to be a helpful diagnostic tool in the management of brain tumors.