• 한국식품영양학회지
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• 제33권3호
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• pp.347-355
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• 2020

Cognitive impairment is considered to be key research topics in the field of neurodegenerative diseases and in understanding of learning and memory. In the present study, we investigated neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts in hydrogen peroxide-induced neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley^® (SD) rat in vivo. Apoptotic cell death in neuroblastic PC12 cell line was induced by hydrogen peroxide for 1 hour at 100 μM. However, mixture of SC and RF treatment prevented peroxide induced PC12 cell death with no neurotoxic effects. For in vivo experiment, the effect of SC and RF extracts on scopolamine-induced cognitive impairment in SD rat was evaluated by spontaneous alternation behavior in Y-Maze test. After 30 min scopolamine injection, the scopolamine-induced rats presented significantly decreased % spontaneous alteration and acetylcholine level, compared to non-induced group. However, treatment of SC+RF extracts rescued the reduced % spontaneous alteration with acetylcholine concentration from hippocampus in scopolamine-induced rats. These results suggested that mixture of SC and RF extract may be a potential natural therapeutic agent for the prevention of cognitive impairment.

• Toxicological Research
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• 제17권
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• pp.257-261
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• 2001

Recently, a traditional medicine called Gouteng-san, which consists of eleven herbs, was reported to be effective in treating vascular dementia with a double-blind, placebo-controlled study. Gout-eng-san is also used for patients with vascular dementia in combination with Si-Wu-Tang. The effect of Gouteng-san and Si-Wu-Tang on deficit of learning behavior was investigated using step-down passive avoidance task in mice. Hot-water extract of Gouteng-san (1.5 and 6 g/kg, p.o.) significantly prolonged the step-down latency shortened by scopolamine. The extract of Uncaria hook (150 mg/kg, p.o.), one of the component herb of Gouteng-san, significantly prevented the decrease in the latency after scopolamine. Hot-water extract of Si-Wu-Tang (1.5 and 6 g/kg of dried herbs, p.o.) prevented dose-dependently scopola-mine-induced disruption qf learning behavior. Si-Wu-Tang also prevented the ischemia-induced deficit of learning behavior. Both hot water extract of peony and angelica (1.5 g/kg, p.o.), which are component herbs qf Si-Wu-Tang, prevented the scopolamine-induced learning behavior deficit. Scopolamine (10 uM) suppressed long-term potentiation (LTP) of population spike in the CA1 region of the rat hippocampal slices. Peoniflorin (0.1~ 1uM) extracted from paeony root significantly ameliorated scopolamine-induced inhibition of LTR These results suggest that improvement of deficit of learning behavior by Gouteng-san and Si-Wu-Tang is mediated by direct and/or indirect activation of the cholinergic system in the brain.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.55-64
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• 2017

Progressive memory impairment such as that associated with depression, stroke, and Alzheimer's disease (AD) can interfere with daily life. In particular, AD, which is a progressive neurodegenerative disorder, prominently features a memory and learning impairment that is related to changes in acetylcholine and abnormal ${\beta}$-amyloid ($A{\beta}$) deposition in the brain. In the present study, we investigated the effects of dehydroevodiamine HCl (DHED) on cognitive improvement and the related mechanism in memory-impaired rat models, namely, a scopolamine-induced amnesia model and a $A{\beta}_{1-42}$-infused model. The cognitive effects of DHED were measured using a water maze test and a passive avoidance test in the memory-impaired rat models. The results demonstrate that DHED (10 mg/kg, p.o.) and Donepezil (1 mg/kg, p.o.) ameliorated the spatial memory impairment in the scopolamine-induced amnestic rats. Moreover, DHED significantly improved learning and memory in the $A{\beta}_{1-42}$-infused rat model. Furthermore, the mechanism of these behavioral effects of DHED was investigated using a cell viability assay, reactive oxygen species (ROS) measurement, and intracellular calcium measurement in primary cortical neurons. DHED reduced neurotoxicity and the production of $A{\beta}$-induced ROS in primary cortical neurons. In addition, similar to the effect of MK801, DHED decreased intracellular calcium levels in primary cortical neurons. Our results suggest that DHED has strong protective effects against cognitive impairments through its antioxidant activity and inhibition of neurotoxicity and intracellular calcium. Thus, DHED may be an important therapeutic agent for memory-impaired symptoms.

• 한국식품영양과학회지
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• 제43권6호
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• pp.799-806
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• 2014

본 연구는 scopolamine으로 유도한 기억력 및 인지기능 감퇴 동물모델에서 비파엽 추출물의 기억력 및 인지기능 개선효과를 평가하기 위해 수행되어졌다. 6주령의 SD-rat(male)을 총 5개 군으로 분리하였으며, 양성대조군으로 donepezil(1 mg/kg b.w.)을 처리하였다. 15일간 24시간 간격으로 EJE를 50, 200 mg/kg b.w. 농도로 전처리(경구투여) 하였으며, 16일째에 농도별로 EJE 및 양성대조군으로서 donepezil을 투여하고 scopolamine을 복강투여(1 mg/kg b.w.) 하였다. Water maze test와 passive avoidance test를 통해 scopolamine으로 유도한 동물모델에서 EJE의 기억력 및 인지능력 개선 효과를 확인한 결과, scopolamine에 의해 감소된 기억력 및 학습능력이 EJE를 투여함으로써 유의적으로 회복 및 증가한 것을 확인할 수 있었다. Scopolamine에 의해 인지능력과 함께 감소된 운동능력의 평가를 위해 수행한 rotarod test 및 vertical pole test에서는 scopolamine의 투여로 감소된 균형감각, 협응력 그리고 grip strength와 같은 운동능력들이 EJE의 투여로 유의적으로 회복된 것을 확인하였다. 또한 scopolamine에 의해 증가한 AchE의 활성과 감소한 Ach의 함량이 EJE의 투여로 각각 개선되었다. 본 연구에서는 이와 같은 결과를 바탕으로 EJE의 scopolamine으로 유도한 동물모델에서 인지능력 개선과 감퇴한 운동능력의 향상 및 cholinergic neurotransmission system의 강화 효과를 확인할 수 있었으며, 이러한 연구 성과들로 비파엽 추출물이 퇴행성뇌질환인 AD 치료와 학습 및 기억력 개선에 있어 효과적인 대안으로서 보다 더 많은 분야에서 연구되기를 바라는 바이다.

• Journal of Acupuncture Research
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• 제35권1호
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• pp.28-36
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• 2018

Background: This study investigated the effects of acupuncture at Sobu (HT8) and Haenggan (LR2) on scopolamine-induced, cognitively impaired rats. Methods: Scopolamine-treated Sprague-Dawley rats were divided into 6 groups; normal, control, HT8, LR2, HT8 + LR2 and sham group. Cognitive impairment was induced by scopolamine, in control, and then in HT8, LR2, HT8 + LR2 and sham groups. Acupuncture treatment was performed at HT8, LR2, HT8 + LR2, and a random acupoint, respectively, every other day for 2 weeks. After each treatment, behavior change was observed and the rats were sacrificed. The change in brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase activity was evaluated by polymerase chain reaction. Results: Latency time to target in Morris Water-Maze test for the HT8 + LR2 group showed a significant decrease compared with control (p<0.05). Target crossing times and time zone ratios in Morris Water-Maze test for HT8 + LR2 group showed a significant increase compared with control (p<0.01). In the Y-Maze test the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase, in the HT8 + LR2 group, showed a significantly increased level compared with control (p<0.05). Neural activity of acetylcholine esterase in HT8 + LR2 group showed a significant decrease compared with the control group (p<0.01), choline acetyltransferase activity in the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Conclusion: Acupuncture at HT8 + LR2 restored scopolamine-induced cognitive impairment, suggesting acupuncture could be an alternative to improve cognitive function.

• 동의생리병리학회지
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• 제36권1호
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• pp.18-22
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• 2022

To investigate effects of cognitive function improvement whether against Taegeuk ginseng on scopolamine-induced memory impairment in rats. All experiments were conducted in three groups: the control group (CTR), the scopolamine 0.4mg/kg (SCP), and the scopolamine (SCP+T) treated with Taegeuk ginseng 100 mg/kg. Taegeuk ginseng 100 mg/kg daily was orally administered for one month and treated with scopolamine was only for 7 consecutive days on the Morris water maze task. 3 weeks after oral administration of Taegeuk ginseng, subjects were performed the Morris water maze test for 8 days and then the open-field exploration test which to assessed for cognitive function improvement. After behavioral testing, subjects were sacrificed and microdissected brains for neurochemical analysis. In the cognitive-behavioral test, long-term administration of Taegeuk ginseng improved spatial navigation learning task compared with the impeded by scopolamine treatment. In neurochemistry, the expression of the synaptic marker PSD95 (postsynaptic density protein 95) was increased in the hippocampus compared to the scopolamine group. Also, brain-derived neurotrophic factor (BDNF) expression was significantly increased in the taegeuk ginseng administration group. These data suggested that long-term administration of taegeuk ginseng might improve cognitive-behavioral functions on hippocampal related spatial learning memory, and it was correlated with neurotropic and synaptic reinforcement. In conclusion, treatment with taegeuk ginseng may positive outcome on learning and memory deficit disorders.

• Archives of Pharmacal Research
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• 제18권5호
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• pp.346-350
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• 1995

To assess the behavior of the various chemicals, such as ethylcholine axiridinium (AF54A), scopolamine and morphine, the chemicals were administered into eitheer rat or mice. And water maze tests were performed before and during drug administration. In AF64A-treated groups (3 nmol/each ventricle), the latencies to escape was significantly increased in both of the pretraining-and posttraining groups. In scopolamine-treatment (2mg/kg, sc) to the pretrained group, the latency to escape was significantly shortened after the acute administration of scopolamine. However in subscute treatment group with scopolamine, the latency to escape was significantly increased. In morphine-treated groups (10 mg/kg, ip), the subacute treatmment with morphine, the latency to escape was not ahcnged. The results indicate that each chemical induces the learning impariment. However the chrmical-induced learning impairment may have different characteristics upon the exposed chemical. Also the results suggest that both the motivation and the retrieval of memory might be impaired by AF64A.

• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.331-338
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• 2013

AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate-induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons.

• 국제물리치료학회지
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• 제4권1호
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• pp.479-487
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• 2013

This study is intended to examine the tDCS and Morris Water maze training in Alzheimer's disease(AD) rats on Tau protein expression. Experiment groups were divided into four groups and assigned 16 rats to each group. Group I was a control group(AD induced by scopolamine); Group II was a experimental control group(AD injured by scopolamine and treatment tacrine); Group III was a group of tDCS application after AD injured by scopolamine; Group IV was a group of morris water maze training after AD injured by scopolamine. In cognition test, the outcome of group II was significantly lower than the groups(p<.001). and group III, IV were significantly low result at 14 days(p<.05). In histological finding, the experimental groups were destroy of micro vessels and finding of cell atropy and swelling. Group III, IV were decreased in degeneration of liver and kidney cells. In immuno- histochemistric response of BDNF and tau protein in hippocampus, BDNF expression of Group II was more increase than the other groups. and increase of BDNF expression was III, IV were higher than group I at 21 days. Tau protein expression of Group II was more decrease than the other groups. and decrease of Tau protein expression was III, IV were lower than group I at 21 days. These result suggest that improved tDCS and morris water maze training after scopolamine induced is associated with dynamically altered expression of BDNF and Tau protein in hippocampus and that is related with cognitive function.

• 동의신경정신과학회지
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• 제16권1호
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• pp.119-128
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• 2005

Objective : The purpose of this study was to estimate the effects of Ramulus et Uncus Uncariae DM fraction on memory enhancing in rats Methods : We oral administered Ramulus et Uncus Uncariae DM fraction to rats then executed passive avoidance test and observed figure of pyramidal neuron on CA1 Results : Findings from our experiments have shown that REUD(>1mg/100g/ml) was effective in memorial improvement. and oral administration of REUD(100mg/100g/ml) for 2 weeks was found to induced the figure of pyramidal neuron on CA1 in rat hippocampus injured by scopolamine. Conclusions : As the result of this study, Decrease of memory induced by injection of scopolamine into rat was also attenuted by REUD, based on passive avoidance test, and REUD was found to reduce the activity of AChE and induced about the CA1 in rat hippocampus. Base on these findings, REUD may be beneficial for the treatment of AD.