• Biomolecules & Therapeutics
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• 제21권4호
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

• 수면정신생리
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• 제20권1호
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• pp.15-21
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• 2013

목 적: 하지불안증후군에서의 인지기능 저하는 흔히 동반되는 수면박탈, 불안, 우울 등에 의해 영향을 받는다. 본 연구의 목적은 투약 받지 않고 있는 한국 노인 인구에서 하지불안증후군과 인지기능 저하와의 관련성을 동반 증상의 영향을 배제하고 살펴보는 것이다. 방 법: 연구대상은 25명의 투약 받고 있지 않은 한국 노인 하지불안증후군 환자군과 나이, 성별, 교육연한에 따라 짝지은 50명의 대조군이다. 모든 연구대상에 대해 CERAD-K 신경심리평가, 중증인지감퇴평가 척도, 전두엽 기능 평가, 그리고 시계 그리기 검사(CLOX)를 포함한 광범위한 인지기능 평가를 시행하였다. 또한 수면의 질 평가를 위해 피츠버그 수면의 질 지수(Pittsburgh Sleep Quality Index, PSQI), 우울증의 평가를 위해 노인우울척도(Geriatric Depression Scale, GDS)를 사용하였다. 결 과: 환자군과 대조군 사이의 PSQI와 GDS 점수의 차이는 없었다. 구성 재인 검사에서 환자군이 대조군에 비해 더 낮은 점수를 보였으며(t=-2.384, p=0.02), 이를 제외한 모든 영역의 인지기능 평가에서 환자군과 대조군의 유의미한 차이는 관찰되지 않았다. 우울감이 있는 대상($GDS{\geq}10$)은 그렇지 않은 군에 비해 언어 유창성, 간이 정신상태 검사, 단어목록기억, 길 만들기 검사, 전두엽 기능 평가의 영역에서 유의한 인지기능 저하를 보였다. 수면의 질이 낮은 대상(PSQI>5)은 그렇지 않은 군에 비해 인지기능 평가의 전 영역에서 차이를 보이지 않았다. 결 론: 본 연구에서 하지불안증후군 환자군을 대조군과 비교한 결과 환자군은 불면과 우울의 영향을 배제하면 비교적 인지기능이 보존된 것으로 관찰되었다. 환자군에서 관찰되었던 시각 인지 영역의 저하는 하지불안증후군에서의 도파민 신경전달계의 장애와 연관하여 해석해 볼 수 있다.

• 생명과학회지
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• 제30권3호
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• pp.250-259
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• 2020

당뇨병은 치매 및 인지기능장애의 주요 위험인자로 알려져 있다. 당뇨병성 말초신경병증은 제2형 당뇨병에서 가장 흔히 발생되는 합병증으로 본 연구는 말초신경병과 인지기능항복 간의 관련성을 확인하기 위함이었다. 2005년부터 2016년 10월 31일까지 동아대학교의료원에 내원한 제2형 당뇨병 환자들을 대상으로 후향적으로 의무기록지를 확인하여 신경전도검사와 신경인지기능검사를 시행한 환자 총 19명을 대상으로 하였다. 총 19명 대상환자의 평균 나이는 71.6±5.0세, 당뇨병 유병기간은 8.4±9.1년, 당화혈색소는 8.1±1.8%였다. 당뇨병성 말초신경병증이 동반된 환자는 전체 19명 중 7명(36.8%)이었다. Korean version of the Mini Mental State Examination (K-MMSE) 검사 결과 총점 24점 미만으로 정의한 인지기능저하를 동반한 환자는 19명 중 8명(42.1%)였다. 당뇨병성 말초신경병증 동반 군과 동반하지 않은 군 간에 K-MMSE 점수와 인지기능저하 동반율은 차이가 없었다. 인지기능저하 동반군과 동반하지 않은 군 간에 DPN 동반 비율도 각각 37.5%와 36.4%로 유의한 차이가 없었다. 인지기능항목과 유의한 상관관계를 보인 변수는 교육 기간이었으며, 교육기간이 길수록 높은 인지기능과 관련이 있었다. 인지항목 중 digit span-forward 만이 신경전도속도(CV)와 유의한 음의 상관관계를 보였다. 결론적으로 제2형 당뇨병 환자에서 교육기간이 길수록 높은 인지기능과 관련이 있었으며, 당뇨병성말초신경병증과 인지기능장애 간에는 유의한 상관 관계가 관찰되지 않았다. 향후 더 큰 규모의 전향적 연구가 필요하다.

• 동의생리병리학회지
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• 제27권6호
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• pp.789-794
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• 2013

Hemorrhage is a devastating type of stroke, accounts for 15-20% of all strokes. This disease can cause cognitive dysfunction with a very high mortality rate. Cupping therapy of Traditional Korean medicine has frequently been used to relieve a variety of diseases or clinical conditions, although not in the memory loss after hemorrhage. This study was designed to evaluate the effects of cupping therapy on learning and memory with Y-maze test, as well as its effects on different molecular changes in hippocampus following the induction of hemorrhage in rats. Cupping, using vacuum cupping machine, was applied at target area for 5 min daily for 7 consecutive days, commencing 1 day after brain impairment. As a result, induction of hemorrhage enhanced memory deficit, suppressed brain-derived neurotrophin factor (BDNF) in the hippocampus. Cupping treatment effectively reversed collagenase-induced cognitive impairment in SD rats which was represented by improvement of spontaneous alterations in Y-maze test. In addition, BDNF expression was enhanced after cupping therapy. The present results suggest that the therapeutic effects of cupping treatment after hemorrhage is involved in expression of BDNF.

• The Korean Journal of Pain
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• 제30권4호
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• pp.258-264
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• 2017

Background: Pulpal pain is one of the most common and severe orofacial pain conditions with considerable adverse effects on physiological processes including learning and memory. Regular exercise is known to be effective on cognitive function as well as pain processing in the central nervous system. Here, the possible effects of regular exercise on pulpal pain response as well as pain-induced changes in learning and memory efficiency in rats were investigated. Methods: Twenty-four male Wistar rats were randomly assigned to the control, capsaicin, exercise, and exercise plus capsaicin groups. Rats in exercise groups were forced to run on a treadmill with a moderate exercise protocol for 4 weeks. Capsaicin was used to induce dental pulp pain. Passive avoidance learning and memory performance was assessed by using a shuttle box apparatus. Results: According to the results, regular exercise could decrease the time course of capsaicin-induced pulpal pain (P < 0.001). Moreover, in capsaicin-treated rats, passive avoidance acquisition was impaired as compared to the control (P < 0.05) and exercise (P < 0.001) groups. Additionally, regular exercise before capsaicin injection could attenuate capsaicin-induced memory impairments (P < 0.05). Conclusions: Taken together, the present data showed that regular exercise has inhibitory effects on capsaicin-induced pulpal pain as well as pain-induced cognitive dysfunction in rats.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제21권3호
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• pp.147-152
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• 2010

Objectives : The purpose of this study was to investigate the deficits in executive function in children with ADHD and anxiety disorder, and further, to characterize executive function deficits among the two groups. Methods : Subjects consisted of 60 children between the ages of 5 and 14 (16 Normal, 24 ADHD, 20 Anxiety Disorder). Neuropsychological tests (KEDI-WISC, CCTT, STROOP, WCST, ROCF) for assessing cognitive and executive function were individually administered to all subjects. Results : There were no significant differences in FSIQ or PIQ among the three groups. However, the ADHD group tended to score lower on the VIQ and subtest of similarity, vocabulary, and digit span tests. The three groups did not significantly differ with respect to CCTT test results. On the STROOP test, the ADHD group showed poor performance on the word, color, and color-word subtests. The three groups did not exhibit significant differences in WCST test results ; however, the anxiety group performed poorly belonging to below 25 percentile rank on perseverative response. On the ROCF test, the ADHD group performed poorly with respect to their organization score and in particular, regarding copy and immediate recall. The anxiety group also performed poorly with regard to organization ; however, this was limited only to immediate recall. Conclusion : Children with ADHD displayed poor inhibition and organizational abilities compared to children with anxiety and normal controls. Further, children with anxiety disorder exhibited low cognitive flexibility and voluntary problem-solving abilities compared to ADHD children and normal controls. Based on these results, we suggest that the characteristics of executive dysfunction in ADHD and anxiety disorder in children are different.

• 생물치료정신의학
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• 제24권3호
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• pp.129-141
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• 2018

Suicide is a behavior that is intended to cause death by itself and requires medical treatment, resulting in suicidal attempt or completion. Suicide causes loss of life, damages the body, costs a lot of medical expenses, and causes families to fall into sorrow and suffering therefore this suicide is a huge loss to family and society. There have been attempts to reduce and prevent suicide by understanding the mechanism of suicide. The mechanism of suicide can be thought of as psychological mechanism and biological mechanism. In the past, if we considered the psychological and biological mechanisms separately, the development of neuroscience now connects and integrates these two. Psychological factors affect biological factors and biological temperaments also affect perception or thinking about the situation and increase psychological vulnerability. Distant factors in suicidal behavior-such as childhood adversity and family and genetic predisposition-increase the lifetime risk of suicide. They alter the response to stress and other processes through changes in gene expression and regulation of emotional and behavioral characteristics. Distant factors affect the biological system and consequently changes in these systems can increase the risk of suicide. In other words, the distal factor does not directly induce suicidal behavior but rather acts indirectly through developmental or mediating factors. These mediating factors are impulsive aggressive and anxious trait, and chronic use of substances. The mechanism of this disorder is the abnormality of the serotonin system and the abnormality of the lipid level. Proximal factors are associated with the onset of suicide events and include changes in the major neurotransmitter systems, inflammatory changes, and dysfunction of glial cells in the brain. A series of studies, including a variety of research methods and postmortem and in-vivo imaging studies, show the impairment of the serotonergic neurotransmitter system and hypothalamic-pituitary-adrenal axis stress response system for suicidal behavior. These disorders lead to suicidal behavior due to difficulty in cognitive control of mood, pessimism, reactive aggression, abnormality in problem solving abilities, excessive response to negative social signals, severe emotional distress, and cognitive dysregulation of suicidal ideation.

• 동의생리병리학회지
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• 제38권1호
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• pp.38-45
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• 2024

To compare and analyze the improvement effects of white ginseng extract, red ginseng extract, and black ginseng extract on cognitive dysfunction and memory impairment caused by scopolamine in rats. In the cognitive behavioral test, the tendency of the SCOP+B group to overcome the escape time delay induced by scopolamine administration was observed, unlike the SCOP group. The frequency on plat form was significantly increased in the group treated with ginseng extracts compared to the SCOP group. As a result of measuring the duration time on goal quadrant, the time spent in the quadrant was significantly increased in the SCOP+B group compared to the SCOP group. In the hippocampus, the SCOP-treated group significantly decreased the activity of AChE compared to the normal group, but the ginseng extract-treated groups significantly increased it compared to the SCOP group. After sacrificing the rats after the behavioral test, the expression of PSD95 protein in the excised brain was significantly decreased in the SCOP group compared to normal, but it was observed that the SCOP+R and SCOP+B groups were significantly increased compared to the SCOP group. CREB1 protein expression was significantly increased in the SCOP+R group, and the expression of Cdk5 was significantly increased in the SCOP+B group. Ginseng extracts significantly restored the memory damaged by scopolamine suggesting that red ginseng increased the expression of CREB1 and PSD95 proteins, and black ginseng increased the protein expression of Cdk5 and PSD95 to induce memory recovery.

• 생물정신의학
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• 제24권2호
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• pp.75-81
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• 2017

Objectives Obsessive-compulsive disorder (OCD) is a chronic and disabling psychiatric disorder. The duration of untreated illness (DUI) has been suggested as one of the predictors of clinical course and outcome in various psychiatric disorders. There is increasing evidence that cognitive dysfunction is associated with the prognosis of OCD. The aim of this study was to investigate the influence of DUI on the neurocognitive functions in patients with OCD. Methods Sixty-two patients with a DSM-IV diagnosis of OCD from the outpatient clinic were included in this study. We defined the short DUI if the DUI was 2-year or less and the long DUI if it was longer than 2-year. Neurocognitive functions were assessed by visuospatial memory function test and 4 subsets of K-WAIS such as vocabulary, arithmetic, block design and picture arrangement. Differences in neurocognitive functions as well as clinical variables between OCD patients with short DUI and those with long DUI were investigated. Correlation analyses were also performed to determine the correlation between DUI and neurocognitive functions. Results Compared with the short DUI group, the long DUI group performed worse in the block design test, which measures executive function. The long DUI group also had a higher level of compulsive symptom severity than the short DUI group. However, the DUI was not correlated with neurocognitive functions. Conclusions Findings in this preliminary study suggest that the long DUI in patients with OCD is associated with more severe executive dysfunction. Studies with larger samples and longitudinal design are needed to further confirm the prognostic role of the DUI in OCD.

• 한국식품과학회지
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• 제51권4호
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• pp.379-392
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• 2019

본 연구에서는 갑주백목 에탄올 추출물(ethanolic extraction from Diospyros kaki (Gabjubaekmok))을 이용하여 in vitro 항산화 활성과 더불어 $A{\beta}$로 유도된 인지기능 저하를 갖는 마우스 모델에서 인지기능 및 뇌 신경세포 보호 효과를 검증하였다. 갑주백목 추출물은 양성대조군과 비교하여 우수한 ABTS 및 DPPH 라디칼 소거활성($IC_{50}=83.30$, $403.88{\mu}g/mL$) 및 MDA 생성 억제 활성($IC_{50}=62.10{\mu}g/mL$)을 보여주었고, in vitro 아세틸콜린 분해효소 억제 활성은 $312.82{\mu}g/mL$의 $IC_{50}$ 값을 나타내었다. 또한, MC-IXC 뇌 신경세포에 과산화수소를 처리하여 산화적 스트레스를 유발시킨 뇌 신경세포 사멸에 대해 보호 효과를 나타냈다. 갑주 백목 추출물의 인지기능 개선 효과를 확인하기 위하여 $A{\beta}$를 사용하여 인지기능 장애 마우스 모델을 수립하였으며, Y-미로, 수동 회피 및 Morris 수중 미로 실험과 같은 행동실험을 통해 인지 및 기억능력에 대한 개선 효과를 나타냈다. 이후 마우스 뇌조직에서의 아세틸콜린 함량의 증가 및 아세틸콜린 분해효소의 활성을 억제함으로써 cholinergic 시스템을 보호하였고, SOD, 환원형 GSH 및 MDA 함량 측정을 통해 항산화 시스템을 개선시켜줌을 확인하였다. 더불어 뇌 조직의 미토콘드리아에서 ROS의 생성 억제, MMP 보호 및 ATP 함량을 회복시켜주었으며, western blot 분석을 통해 $TNF-{\alpha}$와 같은 염증성 사이토카인을 억제시켜 줌으로써 면역반응에 관여하는 JNK의 인산화를 감소시키고 Akt 신호전달을 활성화시켜 세포자동 사멸화를 억제시키는 것으로 확인되었다. 마지막으로 HPLC 분석을 통해서 갑주백목의 주요 생리활성물질이 갈산으로 확인되었다. 이러한 결과를 종합하였을 때, 갑주백목 에탄올 추출물은 뇌 조직에서의 cholinergic 및 항산화 시스템 보호효과를 통해 $A{\beta}$ 처리에 대하여 학습 및 기억 능력을 개선 시킬 수 있는 천연 소재로서의 가능성뿐만 아니라 $A{\beta}$ 및 과산화수소로부터 유발된 산화적 스트레스의 환경에서 뇌신경세포를 보호함으로써 알츠하이머성 질환과 같은 퇴행성 뇌신경질환을 예방할 수 있는 고부가가치 건강기능식품 소재로서의 활용 가능성을 확인하였다.