• 동의생리병리학회지
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• 제25권3호
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• pp.406-416
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• 2011

In this study, we have verified the memory and cognitive enhancing effect of Longanae Arillus, the fruit of Euphoria longana Lamarck, which has been used as a tonic and for the treatment of amnesia, insomnia, and palpitations in oriental medicine. To investigate the effect of Longanae Arillus water extract(LAE) on the memory and cognitive dysfunction, scopolamine (1 mg/kg, i.p.) was injected in C57BL/6 mice and several behavior tests including Y-maze, Morris water-maze, passive avoidance and fear conditioning tests were conducted. Administration of LAE (100 or 200 mg/kg/day, p.o.) effectively improved scopolamine-induced memory impairment and dysfunction. To further determine the possible molecule mechanism of LAE, we have examined the activity and/or mRNA expression of diverse proteins involved in the acetylcholine metabolism. LAE particularly increased the amount of acetylcholine in the cortex which was mediated by suppression of acetylcholine esterase (AchE) activity. In addition, LAE elevated the mRNA expression of muscarinic acetylcholine receptors (mAchRs) without affecting the mRNA levels of choline acetyltransferase (ChAT) and acetylcholine esterase (AchE). In another experiment, LAE effectively inhibited mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-$1{\beta}$ (IL1-${\beta}$), which seemed to be mediated by inhibition of upstream transcription factor NF-${\kappa}B$ and extracellular-regulated kinase 1/2 (ERK1/2). These results demonstrate that Longanae Arillus can increase acetylcholine amount the cortex via regulation of AchE activity as well as mAchRs expression and decrease pro-inflammatory responses via inhibition of NF-${\kappa}B$ signaling pathway, thereby having therapeutic potential to improve memory and cognitive deficit in amnesia.

• 생약학회지
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• 제35권3호통권138호
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• pp.239-243
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• 2004

The ameliorating effect of the MeOH extract of the root of Platycodon grandiflorum on the ethanol-induced cognitive dysfunction in mice was investigated. The total MeOH extract was devided into two fractions, saponin rich fraction and non-saponin fraction. The mice with repeated administration of the total MeOH extract and those with saponin rich fraction both showed a markedly prolongεd latency time upon the step-through test (passive avoidance performance) performed after acute ethanol intoxication, while those with non-saponin rich fraction did not. The results suggest that the extracts from the root of Platycodon grandiflorum exert a beneficial effect on ethanol-induced memory impairment in mice and also suggest that these effects of the extracts might be ascribed to the saponin constituents.

• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• Journal of Preventive Medicine and Public Health
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• 제56권1호
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• pp.31-40
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• 2023

Objectives: This study investigated the effect of cognitive impairment on the association between social network properties and mortality among older Korean adults. Methods: This study used data from the Korean Social Life, Health, and Aging Project. It obtained 814 older adults' complete network maps across an entire village in 2011-2012. Participants' deaths until December 31, 2020 were confirmed by cause-of-death statistics. A Cox proportional hazards model was used to assess the risks of poor social network properties (low degree centrality, perceived loneliness, social non-participation, group-level segregation, and lack of support) on mortality according to cognitive impairment. Results: In total, 675 participants (5510.4 person-years) were analyzed, excluding those with missing data and those whose deaths could not be verified. Along with cognitive impairment, all social network properties except loneliness were independently associated with mortality. When stratified by cognitive function, some variables indicating poor social relations had higher risks among older adults with cognitive impairment, with adjusted hazard ratios (HRs) of 2.12 (95% confidence interval [CI], 1.34 to 3.35) for social nonparticipation, 1.58 (95% CI, 0.94 to 2.65) for group-level segregation, and 3.44 (95% CI, 1.55 to 7.60) for lack of support. On the contrary, these effects were not observed among those with normal cognition, with adjusted HRs of 0.73 (95% CI, 0.31 to 1.71), 0.96 (95% CI, 0.42 to 2.21), and 0.95 (95% CI, 0.23 to 3.96), respectively. Conclusions: The effect of social network properties was more critical among the elderly with cognitive impairment. Older adults with poor cognitive function are particularly encouraged to participate in social activities to reduce the risk of mortality.

• 정신신체의학
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• 제24권2호
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• pp.227-235
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• 2016

연구목적 본 연구의 목적은 자가면역 갑상선장애 환자에서 인지결함의 발생 빈도를 알아보고, 이에 영향 미치는 변인을 규명하며, 특히 갑상선 자가항체와의 연관성을 알아보기 위함이다. 방 법 여성 자가면역 갑상선장애 환자 65명을 대상으로 구조적 면담을 통해서 인구학적 정보를 얻었으며, 한국판 Mini-Mental State Examination(Korean Version of the Mini-Mental State Examination, MMSE-K)와 한국판 Montreal Cognitive Assessment(Korean Version of the Montreal Cognitive Assessment, MoCA-K)를 사용해서 인지기능을 평가하였고, 한국판 Depression Rating Scale(Korean Version of the Hamilton Depression Rating Scale, K-HDRS)를 사용해서 우울증을 평가하였다. 결 과 1) MMSE-K 총점 24점 이하는 7.69%, MoCA-K 총점 22점 이하는 10.77%였다. 인지기능 저하의 빈도는 antimicrosomal 항체 양성군(N=38, 58.46%)과 음성군(N=27) 간에 유의한 차이가 없었다. 2) Antimicrosomal 항체 양성군과 음성군의 변인별 차이를 비교한 결과, 음성군보다 양성군에서 antithyroglobulin 항체 수치, antimicrosomal 항체 수치, TSH 농도는 유의하게 높았고, free T4는 유의하게 낮았다(각각 p<0.05). 3) 자가면역 갑상선장애 환자의 인지기능과 여러 변인의 연관성을 분석한 결과, MMSE-K 검사와 MoCA-K 검사의 총점은 연령, 결혼상태, antithyroglobulin 항체 수치, K-HDRS 총점과 각각 유의한 상관관계가 있었다(각각 p<0.05). 4) 회귀분석 결과, 연령, 교육수준, 갑상선 자가항체, 갑상선기능, 우울증은 자가면역 갑상선장애 환자의 인지기능에 영향을 미치지 않았다. 결 론 본 연구의 결과는 자가면역 갑상선장애 환자의 인지기능과 갑상선 자가항체의 연관성을 지지할 수 없었다.

• Nutrition Research and Practice
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• 제12권3호
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Journal of Korean Neurosurgical Society
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• 제54권6호
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• pp.484-488
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• 2013

Objective : To examine the synergistic effects of both computer-assisted cognitive rehabilitation (CACR) and transcranial direct current stimulation (tDCS) on cognitive function in patients with stroke. Methods : The current double-blind, sham-controlled study enrolled a total of 11 patients who were newly diagnosed with stroke. The patients of the tDCS group (n=6) completed sessions of the Korean computer-assisted cognitive rehabilitation program five times a week for 30 minutes a session during a mean period of 18.5 days concomitantly with the anodal tDCS over the bilateral prefrontal cortex combined with the CACR. The patients of the control group (n=5) also completed sessions of the sham stimulation during a mean period of 17.8 days. Anodal tDCS over bilateral prefrontal cortex (F3 and F4 in 10-20 EEG system) was delivered for 30 minutes at an intensity of 2 mA. Cathode electrodes were applied to the non-dominant arm. All the patients were evaluated using the Seoul Computerized Neuropsychological Test (SCNT) and the Korean Mini-Mental State Examination. Results : Mann-Whitney U test revealed a significant difference between the two groups. The patients of the tDCS group achieved a significant improvement in the post/pre ratio of auditory continuous performance test and visual continuous performance test on the SCNT items. Conclusion : Our results indicate that the concomitant use of the tDCS with CACR to the prefrontal cortex may provide additional beneficial effects in improving the cognitive dysfunction for patients with stroke.

• 대한간호학회지
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• 제51권3호
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• pp.294-304
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• 2021

Purpose: This study aimed to investigate objectively measured physical activity (PA) in institutionalized older adults with mild cognitive impairment (MCI) and to elucidate the influence of autonomic nervous function, salivary cortisol, and PA on cognitive functions based on neurovisceral integration model. Methods: Overall cognitive function was evaluated using the mini-mental state examination (MMSE) and executive function was evaluated using semantic verbal fluency test and clock drawing test. Actigraph for PA, HRV and sAA for autonomous function, and the geriatric depression scale for depression were used. Saliva specimens were collected in the morning for sAA and cortisol. Results: Ninety-eight older adults from four regional geriatric hospitals participated in the study. They took 4,499 steps per day on average. They spent 753.93 minutes and 23.12 minutes on average in sedentary and moderate-to-vigorous activity, respectively. In the multiple regression analysis, lower salivary cortisol level (β = - .33, p = .041) and greater step counts (β = .37, p = .029) significantly improved MMSE score. Greater step count (β = .27, p = .016) also exerted a significant influence on verbal fluency, and greater sAA (β= .35, p = .026) was significantly associated with a better clock drawing test result. Conclusion: Salivary cortisol, sAA and physical activity were significantly associated with cognitive functions. To prevent older adults from developing dementia, strategies are needed to increase their overall PA amount by decreasing sedentary time and to decrease salivary cortisol for cognitive function, and to maintain their sympathetic nervous activity for executive function.

• 대한간호학회지
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• 제53권4호
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• pp.453-467
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• 2023

Purpose: This study investigated the cumulative effects of depressive symptoms on cognitive function over time in community-dwelling older adults. Methods: Data were investigated from 2,533 community-dwelling older adults who participated in the Korean Longitudinal Study of Aging (KLoSA) from the 5th (2014) to the 8th wave (2020). The association between cumulative depressive symptoms and cognitive function was identified through multiple regression analysis. Results: When the multiple regression analysis was conducted from each wave, the current depressive symptoms scores and cognitive function scores were negatively associated, regardless of the waves (B5th = - 0.26, B6th = - 0.26, B7th = - 0.26, and B8th = - 0.27; all p < .001). Further, when all the previous depressive symptoms scores were added as explanatory variables in the 8th wave, the current one (B8th = - 0.09, p < .001) and the previous ones (B5th = - 0.11, B6th = - 0.09, and B7th = - 0.13; all p < .001) were also negatively associated with the cognitive function score. The delta R², which indicates the difference between the model's R² with and without the depressive symptoms scores, was greater in the model with all the previous and current depressive symptoms scores (6.4%) than in the model with only the current depressive symptoms score (3.6%). Conclusion: Depressive symptoms in older adults have a long-term impact. This results in an accumulated adverse effect on the cognitive function. Therefore, to prevent cognitive decline in older adults, we suggest detecting their depressive symptoms early and providing continuous intervention to reduce exposure to long-term depressive symptoms.

• 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.