• Journal of Acupuncture Research
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• v.19 no.6
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• pp.97-110
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• 2002

목적 : 본 연구는 (a) 저빈도 전침의 만성 단발성 관절염에 대한 치료 효과와 (b) 척수에서 동통과 관련되는 지표인 P 물질과 trk A mRNA의 발현조절에 미치는 영향을 연구하기 위해 실행되었다. 방법 : Complete Freund's adjuvant를 실험동물의 우측 경족근관절에 주입하여 관절염을 유발시키고 9주 동안 관찰하였다. 만성 관절염의 최적의 치료조건을 찾기 위하여 각각 세 종류의 경혈(환도, 용천, 족삼리)과 전침자극강도(0.5, 1, 2 mA)를 사용하여, 행동학적 지표로서 동통을 측정하였다. 측정 결과 가장 큰 효과를 나타낸 군을 선택하여 RT-PCR 방법을 사용하여 P 물질 및 trk A mRNA의 변화를 척수 후각과 후근신경절에서 측정하였다. 결과 : 관절의 굴신을 통한 통증 검사와 족과관절 둘레 길이 측정을 통하여 관찰한 결과 원위부에 위치한 환도에 저강도의 자극을 시행한 경우(환도, 0.5 mA)가 가장 우수한 치료 효과를 나타내었다. RT-PCR을 시행한 결과, 환측 후근신경절의 P물질이 관절염 유발 대조군의 경우 정상군에 비해 증가하였고 환도-0.5mA 군에서 다시 감소하는 것을 관찰하였으며, trk A는 관절염 유발군의 경우 척수 후각에서 양측성 증가를 나타내었고 이는 전침치료에 의해 다시 감소되는 것을 관찰하였다. 결론 : 환도 0.5mA의 저빈도 전침은 관절염을 효과적으로 감소시킬 뿐 아니라 관절염으로 증가된 후근신경절의 P 물질과 척수후각의 trk A mRNA 발현을 효과적으로 감소시켰으며, 이는 원위취혈로 선혈된 환도혈의 만성관절염에 대한 치료효과를 분명히 보여준다고 할 수 있다.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.79-97
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• 2010

Background: Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficit. Bee venom acupuncture has traditionally been used to treat several inflammatory diseases and chronic pain conditions. Objectives: The aims of this study were to compare the effects of bee venom (general bee venom, BV) and sweet bee venom (allergen-removed bee venom, SBV) acupuncture on the recovery rate of locomotor function, the expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve, and the expression of c-Fos in the brain following sciatic crushed nerve injury in rats, and to evaluate differences due to administration areas. Method: Walking track analysis, Western blot for BDNF and tyrosine receptor kinase B (TrkB), and immunohistochemistry for c-Fos were performed. In this study, comparative analyses of the effects of BV and SBV acupuncture in relation to administration sites, contralateral side or ipsilateral side, were conducted. Results: In the present result, sciatic function index (SFI) in walking track analysis significantly decreased following sciatic crushed nerve injury. The expressions of BDNF and TrkB in the sciatic nerve increased after induction of sciatic crushed nerve injury. C-Fos expression in the ventrolateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) also increased. BV and SBV acupuncture treatment improved the SFI in walking track analysis. Treatment with SBV at 1mg/kg showed more potent enhancing effect on SFI compared to BV. Treatment with 1mg/kg BV or 1mg/kg SBV acupuncture suppressed the BDNF and TrkB expression in the sciatic nerve. BV and SBV acupuncture treatment also suppressed c-Fos expression in the PVN and vlPAG regions. Treatment with SBV at 1mg/kg showed more potent suppressing effect on c-Fos expression compared to BV when injected into the contralateral side of the injured nerve. Generally we could not find significant difference in the effects between contralateral side and ipsilateral side of the injured nerve. Conclusion: We have shown that BV and SBV acupuncture treatment can be used as the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.

• BMB Reports
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• v.41 no.3
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• pp.242-247
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• 2008

MSS, a comprising mixture of maesil (Prunus mume Sieb. et Zucc) concentrate, disodium succinate and Span80 (3.6 : 4.6 : 1 ratio) showed a significant improvement of memory when daily administered (460 mg/kg day, p.o.) into the normal rats for 3 weeks. During the spatial learning of 4 days in Morris water maze test, both working memory and short-term working memory index were significantly increased when compared to untreated controls. We investigated a molecular signal transduction mechanism of MSS on the behaviors of spatial learning and memory. MSS treatment increased hippocampal mRNA levels of NR2B and TrkB without changes of NR1, NR2A, ERK1, ERK2 and CREB. However, the protein levels of pERK/ERK and pCREB/CREB were all significantly increased to $1.5{\pm}0.17$ times. These results suggest that the improving effect of spatial memory for MSS is linked to MAPK/ERK signaling pathway that ends up in the phosphorylation of CREB through TrkB and/or NR2B of NMDA receptor.

• The Journal of Korean Medicine
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• v.31 no.3
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• pp.66-78
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• 2010

Background: Peripheral nerve injuries are a commonly-encountered clinical problem and often result in a chronic pain and severe functional deficits. Objectives: The aim of this study was to evaluate the effects of acupuncture on the descending pain and the recovery of the locomotor function that follows sciatic crushed nerve injury in rats. Method: In order to assess the effects of acupuncture on the descending pain and functional recovery, we investigated the walking track analysis, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) expression in the sciatic nerve, and on the expressions of c-Fos and nitric oxide synthase in the paraventricular nucleus (PVN) of the hypothalamus and in the ventrolateral periaqueductal gray (vlPAG) region resulting from sciatic crushed nerve injury in rats. Results: Acupuncture treatment at Huantiao (GB30), Yanglingquan (GB34), and Weizhong (BL40) facilitated functional recovery. C-Fos and nitric oxide synthase expressions in the brain and BDNF and TrkB expressions in the sciatic nerve were decreased by acupuncture treatment. The most potent effects of acupuncture were observed at the GB30 acupoint. Conclusion: It is possible that acupuncture can be used for pain control and functional recovery from sciatic nerve injury.

• Journal of Life Science
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• v.21 no.8
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• pp.1134-1141
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• 2011

Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate ${\alpha}$-secretase-mediated A${\beta}$ production which was specifically observed in the brains of subjects with Alzheimer's disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of ${\gamma}$-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor $p75^{NTR}$ and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21may simultaneously induce the up-regulation of $p75^{NTR}$/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of ${\gamma}$-secretase activity.

• Journal of Oriental Neuropsychiatry
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• v.29 no.1
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• pp.57-68
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• 2018

Objectives: To experimentally assess the anti-depressant effects of Gammakdaejo-tang Complex Extracts (GMDJ-Tang) in rats. Methods: Twenty Wistar Hannover (160~170 g) stressed rats were treated with different concentrations of GMDJ-Tang extracts i.e., 0, 62.5 mg/kg, 125 mg/kg, and 250 mg/kg. Chronic mild stress was induced by food deprivation, empty bottles, forced swimming, flickered light, tilt cages, shaking cages, high density breeding, water deprivation, and by soaking the litter cover according to fixed schedule. Blood and brain tissue samples were collected for biochemical analysis. Tests included serotonin and ELISA assays. Results: GMDJ-tang increased the weight of treated rats as well as levels of serotonin, BDNF and TrkB; however, the differences were not significant. In contrast, the extracts significantly decreased blood glucose in stressed rats. GMDJ-tang extracts did not significantly impact Serum AST, ALT, leukocytes, erythrocytes and thrombocytes when comparing treatment groups to control rats. Likewise, hemoglobin, hematocrit and PLT increased in treatment groups following treatment with GMDJ-tang, but this change was without significance. Conclusions: These results suggest that GMDJ-tang can alleviate chronic mild stress in rats, possibly through anti-depressant activity.

• Fisheries and Aquatic Sciences
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• v.26 no.1
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• pp.24-34
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• 2023

Reactive oxygen species (ROS) at high concentrations induce oxidative stress, an imbalanced redox state that is a prevalent cause of neurodegenerative disorders. This study aimed to investigate the protective effect of Capsosiphon fulvescens (CF) extract on oxidative stress-induced impairment of cognitive function in models of neurodegenerative diseases. CF was extracted with subcritical water and several solvents and H₂O₂ (0.25 mM) or aluminum chloride (AlCl₃; 25 µM) as an inducer of ROS was treated in PC12 neuronal cells and zebrafish larvae. All statistical analyses were performed using one-way analysis of variance and Dunnett's test using GraphPad Prism. H₂O₂ and AlCl₃ were found to significantly induce ROS production in PC12 neuronal cells and zebrafish larvae. In addition, they strongly affected intracellular Ca²⁺ levels, antioxidant enzyme activity, brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) signaling, acetylcholinesterase (AChE) activity, and hallmarks of Alzheimer's disease. However, treatment of H₂O₂-induced PC12 cells or AlCl₃-induced zebrafish larvae with CF subcritical water extract at 90℃ and CF water extract effectively regulated excessive ROS production, intracellular Ca²⁺ levels, and mRNA expression of superoxide dismutase, glutathione peroxide, glycogen synthase kinase-3 beta, β-amyloid, tau, AChE, BDNF, and TrkB. Our study suggested that CF extracts can be a potential source of nutraceuticals that can improve the impairment of cognitive function and synaptic plasticity by regulating ROS generation in neurodegenerative diseases.

• Korean Journal of Exercise Nutrition
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• v.16 no.2
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• pp.73-84
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• 2012

Thyroid hormones are important for the development of the brain including the cerebellum. In the present study, we investigated the effect of treadmill exercise on the survival of Purkinje neurons and the activation of astrocytes in the cerebellar vermis of hypothyroidism-induced rat pups. On the day of perinatal 14, pregnant rats were divided into two groups (n = 5 in each group): the pregnant control group and the pregnantmethimazole (MMI)-treated group. For the induction of hypothyroidism in the rat pups, MMI was added to the drinking water (0.02% wt/vol), from the day of perinatal 14 to postnatal 49. After delivery, male rat pups born from the pregnant control group were assigned to the control group. Male rat pups born from the MMI-treated group were divided into the hypothyroidism-induction group, the hypothyroidism-induction with treadmill exercise group, and the hypothyroidism-induction with thyroxine (T4) treatment group (n = 10 in each group). The rat pups in the exercise group were forced to run on a treadmill for 30 min once a day for 4 weeks, starting on postnatal day 22. In the hypothyroidism-induced rat pups, motor coordination was reduced and Purkinje cell death and reactive astrocytes in the cerebellar vermis were increased. Treadmill exercise enhanced motor coordination, increased the survival of Purkinje neurons, down-regulated reactive astrocytes, and enhanced brain-derived neurotrophic factor (BDNF) and receptor tyrosine kinase B (TrkB) expressions in the hypothyroidism-induced rat pups. These results suggest that treadmill exercise has beneficial effects in terms of protecting against thyroid dysfunction by increasing T3 and T4 and the related protein, BDNF, as well as TrkB, inhibition on astrocyte activation and the reduction of Purkinje cell loss regarding the cerebellum in hypothyroidism rat pups.

• Journal of Oriental Neuropsychiatry
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• v.28 no.3
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• pp.287-302
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• 2017

Objectives: To evaluate effects of Resina Dendropanacis Morbiferus (RDM) on stress and sleep hormones when administered to Chronic Mild Stressed (CMS) rats. Methods: Twenty-five healthy rats were randomly divided into 5 groups; Normal, CMS (Control), Resina Dendropanacis Mobiferus 50 mg/kg (RDM 50), 100 mg/kg (RDM 100), and 200 mg/kg (RDM 200). All rats except the normal group were exposed to unpredicted stress conditions such as water deprivation, empty bottles, forced thread mill, etc. according to timetable of CMS for 3 weeks. After a week starting experiments, rats in RDM 50, RDM 100, and RDM 200 groups were fed orally once a day for 2 weeks. Afterward, blood samples were taken from rats to analyze complete blood count, AST, ALT, and glucose. Noradrenalin, GABA and Melatonin were measured by ELISA kit. BDNF, CREB and TrkB were measured by RT-PCT. Results: 1. In Noradrenalin content, RDM 100 and RDM 200 groups revealed significant decrease compared to the control group. 2. In GABA content, RDM 50 and RDM 100 groups revealed significant decrease compared to the control group. 3. In Melatonin content, RDM 100 and 200 groups revealed significant decrease compared to the control group. 4. In Activity of BDNF, RDM 100 and 200 groups revealed significant increase compared to the control group. 5. In Activity of CREB and TrkB, RDM 100 group revealed significant increase compared to the control group. 6. In Erythrocyte and Thrombocyte changes, red blood cells and hematocrit significantly increased in RDM 50 and RDM 200 groups than the control group. Hemoglobin and platelet significantly increased in all experimental groups and the control group. 7. In Weight gain content, all RDM groups revealed insignificant increase compared to the control group. 8. In Glucose content, RDM 50, RDM 100, and RDM 200 groups revealed significant decrease compared to the control group. Conclusions: Results suggest that RDM have effects on stress and sleep hormones when administered to Chronic Mild Stressed (CMS) rats.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.3
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• pp.191-200
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• 2014

We investigated the anxiolytic-like activity of ${\alpha}$-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.