• Mass Spectrometry Letters
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• 제14권3호
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• pp.91-103
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• 2023

As one of the most common mood disorders, numerous studies have shown depression is the main risk factor for non-suicidal self-harm. The pathogenesis of depression is complex, and a comprehensive and rapid measurement of monoamine neurotransmitters and their metabolites will be very helpful in understanding the pathogenesis of depression. Therefore, a rapid and sensitive underivatized liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous monitoring of the levels of ten neurotransmitters and their metabolites in rat serum and limbic system and successfully applied to quantify the changes of neurotransmitter levels in chronic unpredictable mild stress-induced rats. The analytes studied were mainly involved in tyrosine metabolism, tryptophan metabolism, and glutamate cycling pathways, which are important in the pathogenesis of depression. It had been verified the method was sensitive and effective, with satisfactory linearity, and met the requirements of biological sample determination. Levels of neurotransmitters in rat serum, hippocampus, amygdala, prefrontal cortex, striatum, and hypothalamus were determined via the method. The results showed serotonin, dopamine, norepinephrine, and their metabolites were decreased, glutamine was increased, and glutamate was disturbed in chronic unpredictable mild stress-induced depression rats. This method provides a new approach to studying the pathogenesis of depression and other neurological disorders.

• Journal of Animal Science and Technology
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• 제64권4호
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• pp.671-695
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• 2022

The gastrointestinal tract is a complex ecosystem that contains a large number of microorganisms with different metabolic capacities. Modulation of the gut microbiome can improve the growth and promote health in pigs. Crosstalk between the host, diet, and the gut microbiome can influence the health of the host, potentially through the production of several metabolites with various functions. Short-chain and branched-chain fatty acids, secondary bile acids, polyamines, indoles, and phenolic compounds are metabolites produced by the gut microbiome. The gut microbiome can also produce neurotransmitters (such as γ-aminobutyric acid, catecholamines, and serotonin), their precursors, and vitamins. Several studies in pigs have demonstrated the importance of the gut microbiome and its metabolites in improving growth performance and feed efficiency, alleviating stress, and providing protection from pathogens. The use of probiotics is one of the strategies employed to target the gut microbiome of pigs. Promising results have been published on the use of probiotics in optimizing pig production. This review focuses on the role of gut microbiome-derived metabolites in the performance of pigs and the effects of probiotics on altering the levels of these metabolites.

• The Korean Journal of Physiology and Pharmacology
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• 제19권1호
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• pp.15-20
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• 2015

This study was aimed to observe that extremely low frequency magnetic field (ELF-MF) may be relevant to changes of major neurotransmitters in rat brain. After the exposure to ELF-MF (60 Hz, 2.0 mT) for 2 or 5 days, we measured the levels of biogenic amines and their metabolites, amino acid neurotransmitters and nitric oxide (NO) in the cortex, striatum, thalamus, cerebellum and hippocampus. The exposure of ELF-MF for 2 or 5 days produced significant differences in norepinephrine and vanillyl mandelic acid in the striatum, thalamus, cerebellum and hippocampus. Significant increases in the levels of serotonin and 5-hydroxyindoleacetic acid were also observed in the striatum, thalamus or hippocampus. ELF-MF significantly increased the concentration of dopamine in the thalamus. ELF-MF tended to increase the levels of amino acid neurotransmitters such as glutamine, glycine and ${\gamma}$-aminobutyric acid in the striatum and thalamus, whereas it decreased the levels in the cortex, cerebellum and hippocampus. ELF-MF significantly increased NO concentration in the striatum, thalamus and hippocampus. The present study has demonstrated that exposure to ELF-MFs may evoke the changes in the levels of biogenic amines, amino acid and NO in the brain although the extent and property vary with the brain areas. However, the mechanisms remain further to be characterized.

• 생명과학회지
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• 제6권2호
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• pp.142-148
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• 1996

Aloe(Aloe arborescens M$_{ILL}$) has been used as a home medicine for the past several thousand in the world, and has been studied on anti-bacterial and anti-fungal activities, hypotension, atherosclerosis, myocardiac infartion, apoplexy, diabetes as a chronic digenerative disease, tumors, gastrointestinal tract, liver and pancreas' diseases, and genitourinary tract etc. SAMP8 as a learing and memory impairment animal model were fed basic and/or experimental diets with 1.0% freezing dried(FD)-aloe for 8 months. The passive avoidance tests such as acqusition trial and retention test were significantly higher in aloe group than in control group. Grading score of senescence resulted in a marked decreases in aloe group compared with control group. Acetylcholinesterase(AChE) activity was remarkably increased in aloe group compared with control group. Neurotransmitters such as dopamine(DA) and serotonin(5-HT) almost did not change by the feeding of aloe-added diet, but their metabolites such as homovanillic acid(HVA) and 5-hydroxy-indole acetic acid(5-HIAA) in aloe group were significantly increased compared with control group. Therefore, the ratios of HVA/DA and 5-HIAA/5-HT as a ratio of metabolite on neurotransmitter were significantly increased by the feeding of aloe-added diet. These results suggest that aloe vara may be activated acetylcholinesterase, the metabolite of neurotransmitter, and ratios of metabolite on neurotransmitter, resulting ina greater prevention of learning and memory impairments such as Alzheimertype dementia.

• 분석과학
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• 제8권2호
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• pp.215-220
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• 1995

흰쥐 뇌의 선조체로부터 catecholamine, indoleamine 및 대사산물을 동시분석할 수 있는 간편한 방법을 제시하였다. 기기는 ECD를 장착한 HPLC를 사용하였고, 고정상인 $C_{18}$ 컬럼에서, 이 동상은 10mM citric acid, 0.13mM $Na_4EDTA$, 0.58mM SOS를 함유하는 35mM sodium acetate buffer(pH 3.4) : MeOH=85:15가 최적이었다. 이 때 컬럼온도는 $30^{\circ}C$였다. 이 조건으로 dopamine(DA), 3, 4-dihydroxyphenyl acetic acid(DOPAC), homovanilic acid(HVA), 5-hydroxyindole acetic acid(5-HIAA), serotonin(5-HT) 및 noradrenaline(NA)을 미량까지 분석할 수 있었고, 검출한계는 각 성분에 대해 1회 주입당 2~10pg이었다. 이 방법으로 흰쥐의 주령 및 성별에 따른 선조 체내 생체아민과 대사산물의 함량을 비교하였다. 7주령 쥐에서 암컷은 수컷보다 DA와 5-HT의 함량이 유의성 있게 높은 것으로 나타났으며, 주령이 증가함에 따라 암컷에서 DOPAC의 함량이 유의적으로 증가하였다.

• 대한약리학회지
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• 제28권1호
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• pp.1-9
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• 1992

최근에 개발된 생체내 미세투석법을 이용하여 정상혈압 흰쥐(WKY)와 자연발생성 고혈압 흰쥐(SHR)의 후 시상하부에서 세포외액의 모노아민과 그 대사체들을 측정하였다. 뇌정위 고정장치에 의해서 미세투석관을 후 시상하부에 위치시킨후 링거액으로 관류하였다. 모노아민과 그 대사체들은 고속액체 크로마토그라피와 전기화학 검출기를 이용하여 정량하였다. 미세투석관의 시험관내 회수율 검사 결과, 관류액의 유속과 신경화학물질의 상대적 회수율 사이에는 역비례 관계가 있음이 확인되었다. 정상 혈압 흰쥐에서 후 사상하부의 관류액으로 부터 축정한 각종 신경화학물질의 세포외액 농도는 도파민 32nM, 노르에피네프린 50nM, 에피네프린 50nM, 세로토닌 73nM, 3.4-dihydroxyphenylacetic acid(DOPAC) 281 nM, homovanillic acid(HVA) 181 nM, 5-hydroxyindoleacetic acid(5HIAA) 3767nM이었다. 후 시상하부에서 측정된 신경전달물질의 기준치는 WHY와 SHR사이에 차이가 없었으나, DOPAC, HVA, 5HIAA의 기준치는 WKY에 비해서 SHR에서 유의하게 높게 나타났다. 본 연구는 중추 신경화학물질들의 생체내 측정에 미세투석법을 이용할 수 있음을 보여주었다.

• 대한약리학회지
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• 제31권2호
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• pp.153-164
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• 1995

Sympathomimetic amines, especially ephedrine, are a major ingredient in proprietary medications for symptomatic treatment of upper respiratory infections. Their frequent uses can lead to occasional instances of abuse and habituation. The clinical symptoms of ephedrine abuse are similar to that of amphetamine psychosis and resemble closely that of schizophrenia. Because both amphetamine psychosis and schizophrenia are thought to be mediated primarily through the action on catecholamines, ephedrine-induced changes of the biogenic amines can be suspected. However, there were few studies about the central effects of ephedrine because of the milder central action than peripheral. Therefore, the present investigation was undertaken to elucidate the relations between the effects of single or repeated administration of ephedrine on the regional levels of biogenic amines in rat brain and ephedrine-induced CNS stimulation. The male Sprague-Dawley rats weighing $100{\sim}200\;g$ were used. After single or repeated administrations of ephedrine, blocks of tissue were obtained from frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia nigra and cerebellum. The concentration of biogenic amines(norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine(5-HT)) and their metabolites (3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA)) were measured by means of high performance liquid chromatography-electrochemical detector(HPLC-ECD). The results obtained were as follows: 1) In the normal rat, the concentration of norepinephrine was the highest in hypothalamus. Dopamine, DOPAC and HVA were highest in corpus striatum, and 5-HT and 5-HIAA were highest in substantia nigra. Epinephrine was not detectable in any part of the brain tissue. 2) In a single administration of ephedrine, the concentration of DOPAC was decreased in corpus striatum. However, the other biogenic amines and their metabolites were not changed. 3) In repeated administration of ephedrine, the concentration of norepinephrine was decreased in all brain region checked. Dopamine was decreased in corpus striatum and substantia nigra and, increased in hypothalamus, and HVA was decreased in corpus striatum. 5-HT was decreased in all brain region except cerebellum and, 5-HIAA was decreased only in frontal cortex. The ratio of 5-HIAA/5-HT was increased in corpus striatum, thalamus, hypothalamus and substantia nigra. These data indicated that, although a single administration of ephedrine did not change the central neurotransmitters, repeated administration of ephedrine caused the decreases of norepinephrine and 5-HT in the most regions of brain, which may be responsible for the emergence of abnormal behavioral effect after ephedrine abuse.

• Journal of Ginseng Research
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• 제47권4호
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• pp.552-560
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• 2023

Background: Ginseng Radix (Panax ginseng Meyer, Araliaceae) has been used medicinally to treat the brain and nervous system problems worldwide. Recent studies have revealed physiological effects that could potentially benefit cognitive performance or mood. The present study aimed to investigate the antidepressant effects of Korean red ginseng water extract (KGE) and its active component in an unpredictable chronic mild stress (UCMS)-induced animal model and elucidate the underlying mechanisms. Methods: The antidepressant potential of the UCMS model was evaluated using the sucrose preference test and open field tests. The behavioral findings were further corroborated by the assessment of neurotransmitters and their metabolites from the prefrontal cortex and hippocampus of rats. Three doses of KGE (50, 100, and 200 mg/kg) were orally administered during the experiment. Furthermore, the mechanism underlying the antidepressant-like action of KGE was examined by measuring the levels of brain-derived neurotrophic factor (BDNF)/CREB, nuclear factor erythroid 2-related factor 2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) proteins in the prefrontal cortex of UCMS-exposed rats. Results: KGE treatment normalized UCMS-induced depression-related behaviors. Neurotransmitter studies conducted after completing behavioral experiments demonstrated that KGE caused a reduction in the ratio of serotonin and dopamine, indicating a decrease in serotonin and dopamine turnover. Moreover, the expression of BDNF, Nrf2, Keap1 and AKT were markedly increased by KGE in the prefrontal cortex of depressed rats. Conclusion: Our results provide evidence that KGE and its constituents exert antidepressant effects that mediate the dopaminergic and serotonergic systems and expression of BDNF protein in an animal model.

• 생물정신의학
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• 제2권1호
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• pp.3-19
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• 1995

Numerous investigators have conducted extensive investigation in the search for biological markers in psychiatric illness. There are, as a test of q biological approach to the diagnosis of the psychiatric illness, tests for the neurotransmitters, their metabolites, and related enzymes, the neurotransmitter receptors, the neuroendocrine output and response, the membrane transport, peptides and eletrolytes. They are called the biological markers, and they are helpful for the diagnosis or differential diagnosis, choice of treatment or drugs, symptom improvement, predictor of recurrence and anticipation of suicidal attempt. These studies are among the main purposes that are pursued in the neuroscience and based on the potential utility of the biological markers mentioned above. Since 1970's, lots 01 biological markers' studies for the diagnosis, differential diagnosis or subtypes differentiation have been done but varieties of different opinions have been drawn since then through they could explain the charaters of main psychiatric illness(especially schizophrenia and mood disorder). But, the search for biological markers, including displines of neuroendoclinology and neurochemistry(neurotransmitter and thair metabolite), has yielded a number of putative trait merkers and state markers for psychayric illness. This paper aims to anticipate or evaluate the good response to the therapy(Therpeutic response) with lots of markers. Acoording to the diagnosis of lots of diseases or subtypes, we are going to review the papers, mainly concern with 'Is there any Marker' or 'Is any test possible to detect the improvement clinically?' 'Is it possible to predict the recurrence or good prognsis?' or 'Is it possible to select any drug or therapy to bring the good response?' The biological tests to review are mainly the metabolites of catecholamine neurotransmitter, and especially neuroendocrine test based on the knowledge that hormons of the adenohypophysis are influenced by activity of the cerebral or limbic neurons as well as the hypothalamus ones. Among them, author introduced some clinically available tests that are DST, TRH stimulation test(TRHST), GH stimulation test, and the urine MHPG test that can give us the evaluation of the treatment response, the predictor for recurrence or choice of drug that can bring a good response. So author discussed thair potential utility in clarifying, therapeutic, and prognostic issues in psychatric illness. We hope they'll be used and look forward to more active study on the different opinion.

• 생명과학회지
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• 제28권11호
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• pp.1386-1395
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• 2018

최근의 연구결과를 통해서 중추 신경계와 위장관은 장-뇌 축을 따라서 양방향의 상호작용이 일어나고 있다는 것이 분명해지고 있다. 전임상 연구로부터 장내 마이크로비오타가 다양한 생리적 기능을 통해서 중추 신경계의 기능을 조절할 수 있음이 밝혀지고 있다. 폴리페놀 화합물은 과일, 채소, 차, 커피, 와인과 같은 식품에 존재하는 식물 유래의 물질로, 항산화, 항염증, 항균, 면역 조절, 항암, 혈관 확장 및 프리바이오틱스와 유사한 효과를 보유하고 있어 식이를 통해 섭취할 경우 건강에 직접적인 효과를 나타낸다. 최근 들어 폴리페놀 화합물이 인지 기능뿐만 아니라 산화적 스트레스 및 염증성 손상에 대해 작용하는 신경 보호에 유익한 효과를 줄 수 있다는 증거가 보고되고 있다. 본 총설에서는 신경 세포 신호 전달 경로의 자극, 신경 염증, 혈관 기능 및 장내 마이크로비옴과의 상호작용에 따른 폴리페놀 화합물의 신경 보호 효과와 관련된 작용 메커니즘에 대한 일반적인 개요를 제시한다. 폴리페놀 화합물의 대사 산물은 혈액-뇌 장벽을 가로 지르는 신경 전달 물질을 이용하고 뇌 혈관 시스템을 조절하여 작용하거나, 간접적으로 장내 마이크로비오타에 작용한다. 또한, 폴리페놀 화합물은 노화 관련 인지 기능 저하 및 신경 퇴행과 같은 신경계 질환을 다양한 생리 기능을 통해 효과적으로 관리할수 있다는 사실이 제시되고 있다. 폴리페놀 화합물은 신경 염증을 감소시키고 기억과 인지 기능을 향상 시키며 장내 마이크로비오타를 조절하는 능력을 지니고 있기 때문에 신경계 질환의 예방 및 치료에 있어 잠재적인 기능성 식품으로 주목 받을 것으로 기대된다.