• Journal of Ginseng Research
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• 제36권4호
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• pp.403-410
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• 2012

The current inquiry was conducted to assess the change in sleep architecture after long periods of administration to determine whether ginseng can be used in the therapy of sleeplessness. Following post-surgical recovery, red ginseng extract (RGE, 200 mg/kg) was orally administrated to rats for 9 d. Data were gathered on the 1st, 5th, and 9th day, and an electroencephalogram was recorded 24 h after RGE administration. Polygraphic signs of unobstructed sleep-wake activities were simultaneously recorded with sleep-wake recording electrodes from 11:00 a.m. to 5:00 p.m. for 6 h. Rodents were generally tamed to freely moving polygraphic recording conditions. Although the 1st and 5th day of RGE treatment showed no effect on power densities in nonrapid eye movement (NREM) and rapid eye movement (REM) sleep, the 9th day of RGE administration showed augmented ${\alpha}$-wave (8.0 to 13.0 Hz) power densities in NREM and REM sleep. RGE increased total sleep and NREM sleep. The total percentage of wakefulness was only decreased on the 9th day, and the number of sleep-wake cycles was reduced after the repeated administration of RGE. Thus, the repeated administration of RGE increased NREM sleep in rats. The ${\alpha}$-wave activities in the cortical electroencephalograms were increased in sleep architecture by RGE. Moreover, the levels of both ${\alpha}$- and ${\beta}$-subunits of the ${\gamma}$-aminobutyric acid $(GABA)_A$ receptor were reduced in the hypothalamus of the RGE-treated groups. The level of glutamic acid decarboxylase was over-expressed in the hypothalamus. These results demonstrate that RGE increases NREM sleep via $GABA_A$ergic systems.

• 생명과학회지
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• 제17권7호통권87호
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• pp.970-975
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• 2007

국내해안의 젓갈과 김치류로부터 86종의 GABA 생산균주를 분리하였다. 분리된 균주들을 Thin layer chromatography를 이용하여 GABA 생성능이 우수한 AML15, AML45-1, AML72의 3종의 균주를 선발하였다. 선별된 3종의 균주의 아미노산 분석 결과 GABA 생성능이 가장 우수한 AML15 균주를 본 실험에 사용하였다. AML15의 분류학적 위치를 규명하기 위하여 16S ribosomal DNA 영역의 부분염기서열 분석을 실시하였다. 165 rDNA 분석결과 Lactobacillus brevis ATCC 367과 99%의 유사도를 나타내어 L. brevis AML15로 명명하였다. MRS 배지에 최종 전환 농도로 설정된 5%(w/v) monosodium glutamic acid를 첨가하고 배지의 초기 pH를 4.0, 5.0과 6.0으로 조정하여 배양한 결과 배지의 초기 pH가 5.0일 때 GABA 생성능이 가장 높게 조사되었다. GABA 생산배지에 GAD 효소활성에 조효소로 작용하는 PLP를 0. 10. 50과 100 ${\mu}M$의 농도로 첨가하여 아미노산 분석결과 PLP를 10${\mu}M$ 첨가하였을 때 10,424 $nM/{\mu}$l의 GABA가생산되었다. PLP를 첨가하지 않았을 때보다 PLP 첨가 후 GABA 생성이 증가됨을 확인할 수 있었다.

• 한국발생생물학회지:발생과생식
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• 제14권1호
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• pp.35-41
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• 2010

Mammalian reproduction is regulated by a feedback circuit of the key reproductive hormones such as GnRH, gonadotropin and sex steroids on the hypothalamic-pituitary-gonadal axis. In particular, the onset of female puberty is triggered by gain of a pulsatile pattern and increment of GnRH secretion from hypothalamus. Previous studies including our own clearly demonstrated that genistein (GS), a phytoestrogenic isoflavone, altered the timing of puberty onset in female rats. However, the brain-specific actions of GS in female rats has not been explored yet. The present study was performed to examine the changes in the activities of GnRH neurons and their neural circuits by GS in female rats. Concerning the drug delivery route, intracerebroventricular (ICV) injection technique was employed to eliminate the unwanted actions on the extrabrain tissues which can be occurred if the testing drug is systemically administered. Adult female rats (PND 100, 210-230 g BW) were anaesthetized, treated with single dose of GS ($3.4{\mu}g$/animal), and sacrificed at 3 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly raised the transcriptional activities of enhanced at puberty1 (EAP-1, p<0.05), glutamic acid decarboxylase (GAD67, p<0.01) which are known to modulate GnRH secretion in the hypothalamus. However, GS infusion could not change the mRNA level of nitric oxide synthase 2 (NOS-2). GS administration significantly increased the mRNA levels of KiSS-1 (p<0.001), GPR54 (p<0.001), and GnRH (p<0.01) in the hypothalami, but decreased the mRNA levels of LH-$\beta$ (p<0.01) and FSH-$\beta$ (p<0.05) in the pituitaries. Taken together, the present study indicated that the acute exposure to GS could directly activate the hypothalamic GnRH modulating system, suggesting the GS's disrupting effects such as the early onset of puberty in immature female rats might be derived from premature activation of key reproduction related genes in hypothalamus-pituitary neuroendocrine circuit.

• Biomolecules & Therapeutics
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• 제15권3호
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• pp.175-181
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• 2007

Zizyphi Spinosi Semen (ZSS), a traditional Chinese folk medicine, has been used for treatment of insomnia and anxiety. This experiment was performed to investigate the anxiolytic-like effect of methanol extract of ZSS (MEZSS) in mice by using the experimental paradigms of anxiety and compared with that of a known anxiolytic, diazepam. In the elevated plus-maze test, it showed that MEZSS (100 mg/kg, p.o.) and diazepam (2.0 mg/kg, p.o.) increased the percentage of time spent on the open arms and the number of open arms entries. MEZSS (50, 100 and 200 mg/kg, p.o.) and diazepam (0.5 mg/kg, p.o.) significantly increased the number of head dips compared with that of control group in the hole-board test. However, MEZSS has no effect on decreasing the locomotor activity, while diazepam (2.0 mg/kg, p.o.) significantly inhibited locomotor activity. MEZSS did not decrease the strength force in the grip strength test, either. In addition, GABAergic involvements were also investigated to understand the possible mechanisms. $GABA_{A}$ receptors subunits and glutamic acid decarboxylase (GAD) were not over expressed, compared with that of the saline group. We also found that MEZSS did not increase chloride influx in cultured cerebellar granule cells. It is concluded that MEZSS might have anxiolytic-like effects, but these effects might not be mediated by GABAergic transmission.

• 대한유전성대사질환학회지
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• 제14권2호
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• pp.191-194
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• 2014

사립체 근병증은 사립체 호흡 사슬의 장애로 인한 것으로 내분비계 관련 증상이 흔히 동반되고 그 중 당뇨병이 상대적으로 높은 빈도를 보인다고 알려져 있다. 사립체 근병증에서의 당뇨병은 사립체 기능 장애로 인한 인슐린 분비의 결함으로 발생하고, 대개 인슐린 의존성이나 당뇨병성 케톤산증으로 발현하거나 자가 항체가 검출되는 경우는 드물다. 저자들은 사립체 근병증 환자에서 당뇨병성 케톤산증으로 발현하고 Anti-GAD antibody와 Anti-insulin auto-antibody가 모두 양성으로 확인된 인슐린 의존성 당뇨병을 진단하였기에 이를 기존의 문헌과 비교하여 보고하는 바이다.

• Clinical and Experimental Reproductive Medicine
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• 제31권1호
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• pp.19-27
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• 2004

Objective: This study was to examine the in vitro neural cell differentiation patterns of human embryonic stem (hES) cells following treatment of various neurotrophic factors [basic fibroblast growth factor (bFGF), retinoic acid (RA), brain derived neurotrophic factor (BDNF) and transforming growth factor (TGF)-$\alpha$], particulary in dopaminergic neuron formation. Methods: The hES cells were induced to differentiate by bFGF and RA. Group I) In bFGF induction method, embryoid bodies (EBs, for 4 days) derived from hES were plated onto gelatin dish, selected for 8 days in ITSFn medium and expanded at the presence of bFGF (10 ng/ml) for another 6 days followed by a final differentiation in N2 medium for 7, 14 and 21 days. Group II) For RA induction, EBs were exposed of RA ($10^{-6}M$) for 4 days and allowed to differentiate in N2 medium for 7, 14 and 21 days. Group III) To examine the effects of additional neurotrophic factors, bFGF or RA induced cells were exposed to either BDNF (10 ng/ml) or TGF-$\alpha$ (10 ng/ml) during the 21 days of final differentiation. Neuron differentiation and dopamine secretion were examined by indirect immunocytochemistry and HPLC, respectively. Results: The bFGF or RA treated hES cells were resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with BDNF or TGF-$\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression of a dopaminergic neuron marker, compared to control (p<0.05). In contrast, no effect was observed on the rate of mature neuron (NF-200) or glutamic acid decarboxylase-positive neurons. Immunocytochemistry and HPLC analyses revealed the higher levels of TH expression (20.3%) and dopamine secretion (265.5 $\pm$ 62.8 pmol/mg) in bFGF and TGF-sequentially treated hES cells than those in $\alpha$ RA or BDNF treated hES cells. Conclusion: These results indicate that the generation of dopamine secretory neurons from in vitro differentiated hES cells can be improved by TGF-$\alpha$ addition in the bFGF induction protocol.

• Archives of Pharmacal Research
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• 제22권5호
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• pp.437-447
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• 1999

Type I diabetes, also known as insulin-dependent diabetes mellitus (IDDM) results from the destruction of insulin-producing pancreatic $\beta$ cells by a progressive $\beta$ cell-specific autoimmune process. The pathogenesis of autoimmune IDDM has been extensively studied for the past two decades using animal models such as the non-obese diabetic (NOD) mouse and the Bio-Breeding (BB) rat. However, the initial events that trigger the immune responses leading to the selective destruction of the $\beta$ cells are poorly understood. It is thought that $\beta$ cell auto-antigens are involved in the triggering of $\beta$ cell-specific autoimmunity. Among a dozen putative $\beta$ cell autoantigens, glutamic acid decarboxylase (GAD) has bee proposed as perhaps the strongest candidate in both humans and the NOD mouse. In the NOD mouse, GAD, as compared with other $\beta$ cell autoantigens, provokes the earliest T cell proliferative response. The suppression of GAD expression in the $\beta$ cells results in the prevention of autoimmune diabetes in NOD mice. In addition, the major populations of cells infiltrating the iselts during the early stage of insulitis in BB rats and NOD mice are macrophages and dendritic cells. The inactivation of macrophages in NOD mice results in the prevention of T cell mediated autoimmune diabetes. Macrophages are primary contributors to the creation of the immune environment conducive to the development and activation of $\beta$cell-specific Th1-type CD4+ T cells and CD8+ cytotoxic T cells that cause autoimmune diabetes in NOD mice. CD4+ and CD8+ T cells are both believed to be important for the destruction of $\beta$ cells. These cells, as final effectors, can kill the insulin-producing $\beta$ cells by the induction of apoptosis. In addition, CD8+ cytotoxic T cells release granzyme and cytolysin (perforin), which are also toxic to $\beta$ cells. In this way, macrophages, CD4+ T cells and CD8+ T cells act synergistically to kill the $\beta$ cells in conjunction with $\beta$ cell autoantigens and MHC class I and II antigens, resulting in the onset of autoimmune type I diabetes.

• 동아시아식생활학회지
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• 제17권2호
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• pp.205-212
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• 2007

This study was designed to investigate a natural medicinal multi-plants extract (BG515), which consisted of multi extracts of Mori folium, Rehmannia glutinosa Liboschitz, Dioscorea japonica, Lycii fructus, and Astragalus radix, on blood glucose, insulin levels, and serum malondialdehyde (MDA) concentrations in streptozotocin-induced diabetic rats. Streptozotocin (STZ) induces a type 1 diabetes mellitus in rats. Type 1 is usually characterized by the presence of islet cell autoantibodies (ICA), autoantibodies to insulin (IAA), and autoantiboides to glutamic acid decarboxylase (GAD), which identify the autoimmune process that leads to $\beta-cell$ destruction. Thirty-five male Sprague-Dawley (SD) rats weighing $150\sim170g$ each (6 weeks old) were randomly divided into one control (Group A) and 4 STZ-induced diabetic groups, and were subjected to one of the following treatment for 12 weeks. Groups A and B were fed basal diets and Group C, D, and E received the same diets as groups A and B, but with supplements of 150 mg/kg, 300 mg/kg, and 600 mg/kg of BG515 orally for 12 weeks, respectively. Diabetes was induced in Groups B, C, D, and E by intravenous injection of 45 mg/kg of STZ per body weight in sodium citrate buffer (pH 4.5) via the tail vein. In the BG515 groups, we found increases in serum insulin levels, compared to the STZ-control group, but these data were not significant. In contrast, blood glucose and serum MDA concentrations decreased in the BG515 groups compare to the STZ-control group. At the 5th week, in all the BG515 administered groups, there were decreases in serum blood glucose levels compared to the STZ- control group, and this activity was very strong in the BG515-1 group at the 12th week. These results suggest that natural bio-complex compounds (BG515) may slightly suppress STZ-induced changes in serum MDA concentration via the maintenance of serum insulin levels, due to the prevention of $\beta-cell$ and glucagon destruction by STZ.

• Clinical and Experimental Pediatrics
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• 제53권3호
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• pp.414-419
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• 2010

목 적 : 제 1형 당뇨병에서 보이는 자가 항체와 질환의 진행에 따른 변화와의 관계는 여러 연구에서 보고되었고, 항체가가 높을수록 진행의 정도가 급격하였다. 따라서 진단 당시에 시행한 자가 항체의 발현 여부에 따라 임상 발현 정도가 다를 것으로 생각하여, 자가 항체 유무에 따라 임상 양상과 검사 소견의 차이가 있는지를 확인하고자 하였다. 방 법 : 1999년 4월부터 2008년 3월까지 3개 대학병원에 내원하여 제 1형 당뇨병으로 진단받은 18세 미만 환자 중 처음 진단 당시에 췌장 자가 항체인 GADA 혹은 IAA의 검사를 시행하였던 96명에서 진단 당시 시행한 혈액 검사 및 임상 양상을 항체 그룹에 따라 나누어 비교 분석하였다. 결 과 : GADA는 87명의 환자에서 검사가 이루어 졌고, 이 중 48명(55.2%)에서 양성을 보였다. IAA는 88명 중 35명(39.8%)이 양성을 보였다. 두가지 항체를 모두 검사한 환자는 83명이었고, 이 중 22.8%에서 두 항체가 모두 검출되었고, 38.6%에서는 모두 음성을 보였다. 1가지 이상의 항체를 갖는 환자군에서는 음성군에 비해 비교적 어린 나이에 당뇨병이 발생하였고, 낮은 BMI, 낮은 혈청 교정 Na 수치 및 낮은 혈청 오스몰농도를 보였다(P <0.05). 자가 항체 중 GADA 양성군과 음성군 사이의 검사소견 상에서도 같은 차이를 보였다. 그러나 IAA 항체 유무에 따른 비교에서는 발생 연령이외는 두 군사이에 임상 및 검사소견상 유의한 차이를 볼 수 없었다. 결 론 : 항체 양성군과 음성군 사이에서 보이는 대사적 결과의 차이는 비교적 적었으나 GADA와 IAA 항체의 양성율은 어린 연령에서 높았다. 따라서 비교적 어린 연령에 발생하는 1형 당뇨병에서는 질환을 처음으로 진단할 때자가 항체 유무를 확인하고, 만약 항체가 확인되면 향후 집중적인 인슐린 치료를 시행하여 보다 좋은 예후를 유도하는데 도움이 될 수 있을 것이다.