• Archives of Pharmacal Research
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• 제28권3호
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• pp.335-342
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• 2005

The effects of ginsenosides Rg$_3$(R) , Rg$_3$(S) and Rg$_5$/Rk$_1$ (a mixture of Rg$_5$ and Rk$_1$ 1:1, w/w), which are components isolated from processed Panax ginseng C.A. Meyer (Araliaceae), on memory dysfunction were examined in mice using a passive avoidance test. The ginsenosides Rg3(R), Rg3(S) or Rg$_5$/Rk$_1$, when orally administered for 4 days, significantly ameliorated the memory impairment induced by the single oral administration of ethanol. The memory impairment induced by the intraperitoneal injection of scopolamine was also significantly recovered by ginsenosides Rg3(S) and Rg$_5$/Rk$_1$. Among the three ginsenosides tested in this study, Rg$_5$/Rk$_1$ enhanced the memory function of mice most effectively in both the ethanol­and scopolamine-induced amnesia models. Moreover, the latency period of the Rg$_5$/Rk$_1$­treated mice was 1.2 times longer than that of the control (no amnesia) group in both models, implying that Rg$_5$/Rk$_1$ may also exert beneficial effects in the normal brain. We also evaluated the effects of these ginsenosides on the excitotoxic and oxidative stress-induced neuronal cell damage in primary cultured rat cortical cells. The excitotoxicity induced by glutamate or N­methyl-D-aspartate (NMDA) was dramatically inhibited by the three ginsenosides. Rg$_3$(S) and Rg$_5$/Rk$_1$ exhibited a more potent inhibition of excitotoxicity than did Rg$_3$(R). In contrast, these ginsenosides were all ineffective against the H$_2$O$_2$- or xanthine/xanthine oxidase-induced oxidative neuronal damage. Taken together, these results indicate that ginsenosides Rg$_3$(S) and Rg$_5$/Rk$_1$ significantly reversed the memory dysfunction induced by ethanol or scopolamine, and their neuroprotective actions against excitotoxicity may be attributed to their memory enhancing effects.

• 재활치료과학
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• 제10권4호
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• pp.39-52
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• 2021

목적 : 본 연구의 목적은 기억력 장애를 가진 성인 환자를 대상으로 기억력 향상을 위한 작업치료 중재를 수행한 단일대상연구의 특성을 확인하고 질적 수준을 알아보는 것이다. 연구방법 : 본 연구는 2011년부터 2020년까지 기억력 향상 작업치료 중재 연구 중 단일대상연구 설계를 적용한 총 6편의 논문을 분석한 문헌연구로, 연구내용에 대한 일반적 특성 및 연구방법의 질적 수준을 분석하였다. 결과 : 분석대상의 질적 수준은 66.7%(4편)가 중간 수준이었고 33.3%(2편)는 높은 수준이었으며, 낮은 수준의 연구는 없었다. 단일대상연구 설계 유형은 모두 반전설계로 ABA가 가장 많았다. 대상자는 뇌졸중, 치매, 경도인지장애 환자였으며, 대상자 수는 1~3명이었다. 독립변수는 오차배제훈련, 어플리케이션 활용 중재, 전산화인지훈련, 시간차회상훈련이었다. 종속변수는 공통변수인 기억력과 함께 집중력, 뇌파변화, 수단적 일상생활활동 및 우울이었다. 중재시간은 30~40분, 중재회기는 6~15회기였으며, 총 연구기간은 3~8주로 다양하였다. 중재 결과 모든 연구에서 중재 후 종속변수가 향상된 것으로 보고되었다. 결론 : 기억력훈련에 대한 단일대상연구 적용 작업치료 중재 연구들은 모두 중간 이상의 질적 수준을 보여 임상에서 적용 시 근거기반자료로 의의가 있으며, 기억력 향상에 효과적인 연구들이라는 것을 확인하였다.

• 한국식생활문화학회지
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• 제36권6호
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• pp.633-639
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• 2021

Raphanus sativus var. hortensis f. raphanistroides Makino (Korean wild radish [WR]) are root vegetables belonging to the Brassicaceae family. These radish species mostly grow in sea areas in Asia, where they have been traditionally used as a medicinal food to treat various diseases. To investigate the effect of WR on neuronal cell death in SH-SY5Y cells, beta-amyloid was used to develop the cell death model. WR attenuated neuronal cell death in SH-SY5Y and regulated the mitogen-activated protein kinase (MAPK) signaling. WR extract also inhibited acetylcholinesterase inhibitor activity. Additionally, the WR treatment group ameliorated the behavior of the memory-impaired mice in a scopolamine-induced mouse model. In the behavior test, WR treated mice showed shorter escape latency and swimming distance and improved the platform-crossing number and the swimming time within the target quadrant. Furthermore, WR prevented histological loss of neurons in hippocampal CA1 regions induced by scopolamine. This study shows that WR can prevent memory impairment which may be a crucial way for the prevention and treatment of memory dysfunction and neuronal cell death.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.176-183
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• 2014

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta ($A{\beta}$) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in $A{\beta}$-induced neurotoxicity. In mice with $A{\beta}$-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an $IC_{50}$ value of $79.7{\mu}g/ml$ for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제28권2호
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• pp.123-131
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• 2017

Objectives: Executive dysfunction including working memory deficit has been suggested to be one of the major neuropsychological etiologies of attention-deficit hyperactivity disorder (ADHD). The purpose of this study was to investigate the augmentative effects of Cogmed working memory training on the symptoms and neurocognitive functions in medicated children and adolescents with ADHD. Methods: Twenty-five children with ADHD, aged 7 to 19 years, taking ADHD medication participated in this study. The participants were trained for 5 weeks with a commercially available and computerized working memory program ($Cogmed^{(R)}$) without any changes to their medication. The Korean version of the ADHD Rating Scale, Clinical Global Impression Scale, and Comprehensive Attention Test were administered before training and 4 weeks and 7 months after training, respectively. Results: After completing the training, the clinical symptoms and function, rated by the parents and clinician, were improved. In addition, the level of commission errors was significantly reduced in the selective attention (visual/auditory) task, sustained attention to response task, and flanker task. The untrained visuospatial short-term memory and working memory were also improved. These effects were still observed 7 months after the training. Conclusion: Cogmed working memory training can be a promising training option for the additional improvement of the symptoms and deficits in working memory and response inhibition in medicated children with ADHD.

• 생물정신의학
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• 제16권4호
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• pp.238-245
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• 2009

Objectives : Mild Alzheimer's disease(AD) is uncertain to be related to visuospatial working memory subsystem dysfunction. We used the self ordered pointing test(SOPT) to find the characteristics of visuospatial working memory in mild AD. Methods : We compared the visuospatial working memory abilities of 20 patients with mild AD and 20 normal elderly controls(NC) using SOPT, of which stimuli consisted of two stimuli types(A : abstract, C : concrete) and two stimuli numbers(8 and 12). Therefore, working memory was tested using C8, C12, A8, and A12 stimuli conditions in SOPT. Mixed-model ANOVA was conducted with the AD and NC groups as between-subjects factor, with stimuli types and stimuli numbers as the within-subjects factors and with SOPT error rates as the dependent variable. Results : The AD group showed higher error rates in SOPT than the NC group. The NC group showed low error rates in concrete stimuli than in abstract stimuli and in small stimuli numbers than in large stimuli numbers. And the AD group showed no differences between stimuli types or stimuli numbers. Conclusion : AD patients showed a poor performance in visuospatial working memory using concrete stimuli. The result suggests that there is a non-transformation from visual input to phonological working memory in AD. Patients with AD showed a poor performance although in small stimuli number condition of SOPT. It suggests that in AD, visuospatial working memory is not working well although in low central executive loads.

• Toxicological Research
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• 제31권1호
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• pp.17-23
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• 2015

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout ($Hfe^{-/-}$) and wild-type ($Hfe^{+/+}$) mice were intranasally-instilled with manganese chloride ($MnCl_2$ 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in $Hfe^{+/+}$ mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, $Hfe^{-/-}$ mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in $Hfe^{+/+}$ mice, but not in $Hfe^{-/-}$ mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

• Journal of Ginseng Research
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• 제33권2호
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• pp.132-138
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• 2009

Previous studies suggest that even low-dose irradiation can lead to progressive cognitive decline and memory deficits, which implicates, in part, hippocampal dysfunction in both humans and experimental animals. In this study, whether red ginseng (RG) could attenuate memory impairment was investigated through a passive-avoidance and object recognition memory test, as well as the suppression of hippocampal neurogenesis, using the TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) in adult mice treated with a relatively low-dose exposure to gamma radiation (0.5 or 2.0 Gy). RG was administered intraperitonially at a dosage of 50 mg/kg of body weight, at 36 and 12 h pre-irradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg! kg of body weight/day for seven days before autopsy. In the passive-avoidance and object recognition memory test, the mice that were trained for one day after acute irradiation (2 Gy) showed significant memory deficits compared with the sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 12 h after irradiation. In addition, the number of Ki-67- and DCX-positive cells was significantly decreased. RG treatment prior to irradiation attenuated the memory defect and blocked apoptotic death as well as a decrease in the Ki-67- and DCX-positive cells. RG may attenuate memory defect in a relatively low-dose exposure to radiation in adult mice, possibly by inhibiting the detrimental effect of irradiation on hippocampal neurogenesis.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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• pp.417-424
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• 2017

Alzheimer's disease (AD) is neurodegenerative disease, characterized by the progressive decline of memory, cognitive functions, and changes in personality. The major pathological features in postmortem brains are neurofibrillary tangles and amyloid beta ($A{\beta}$) deposits. The majority of AD cases are sporadic and age-related. Although AD pathogenesis has not been established, aging and declining mitochondrial function has been associated. Mitochondrial dysfunction has been observed in AD patients' brains and AD mice models, and the mice with a genetic defect in mitochondrial complex I showed enhanced $A{\beta}$ level in vivo. To elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells transfected with DNA constructs expressing human amyloid precursor protein (APP) or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the level of $A{\beta}$ protein in comparison with control. When complex I was inhibited by rotenone, the increase of ROS level was remarkably higher in the cells overexpressing APP-swe compared to control. The number of dead cell was significantly increased in APP-swe-expressing cells by complex I inhibition. We suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.

• 한국전문물리치료학회지
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• 제12권3호
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• pp.67-73
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• 2005

Prospective memory (PM) is related to remember to carry out a previously intented behaviour. The purpose of this study was to develop a paradigm for measuring PM function to diagnosis in mild cognitive impairment 1 or brain injury in patients 2. among brain injured patients Thirty-eight normal healthy subjects participated in current study. The paradigm was composed of four conditions: a baseline and three intention conditions (expectation, execution 1 and 2). In the expectation condition, subjects were asked to make a new response to intented stimuli during ongoing task, but the intented stimuli never occurred. In the execution 1 (one type of expected stimulus) and 2 (two types of expected stimuli), the intended stimuli did occur in 20% of trials. The reaction time and error rate were calculated in each condition. Repeated measures using ANOVA of subject's mean reaction times (RTs) and mean error rates (ERs) showed main effects of conditions during ongoing task. The comparison of PM tasks in executive condition 1 and 2 also showed significance in RTs and ERs. This paradigm reflects sufficiently the performance of prospective memory function during ongoing task in normal individuals. Thus, we suggest that the paradigm will be helpful to study neural network of PM function using brain imaging techniques and diagnosis of PM dysfunction.