• Molecules and Cells
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• 제38권9호
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• pp.796-805
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• 2015

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced $[Ca^{2+}]_i $ transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated $[Ca^{2+}]_i $ transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 1 2 weeks) also significantly attenuated amyloid-${\beta}$ protein ($A{\beta}$)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to $A{\beta}$ and could be utilized for AD prevention or therapy.

• 대한영상의학회지
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• 제85권1호
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• pp.184-196
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• 2024

목적 인지기능 저하를 진단하기 위해서 자기공명영상을 이용한 영상 소견의 진단능을 평가하였다. 대상과 방법 총 138명의 주관적인 인기지능 저하를 호소하며, MRI 검사를 시행한 환자를 대상으로 하였다. 이 환자 그룹은 신경정신학적 평가를 통해 알츠하이머군과 비알츠하이머군으로 분류되었다. 우리는 이들의 white matter hyperintensity와 cerebral microbleed를 평가하였으며, Kruskal- Wallis test를 통해 그룹 간의 비교를, receiver operating characteristic (이하 ROC)를 통해 영상학적 소견의 진단능을 평가하였다. 결과 인지기능 정상인 경우와 경도인지장애 환자와 비교해서 알츠하이머 환자에서 엽 혹은 심부 미세출혈이 빈번하게 관찰되었으며, 심한 심부 혹은 뇌실주위, 전체 백질 신호강도 또한 인지기능 정상에 비해서 알츠하이머 환자에서 많이 관찰되었다. 알츠하이머 환자와 다른 환자 그룹(정상 혹은 경도인지장애)을 비교할 때 엽미세출혈과 뇌실주위 뇌백질 신호강도 증가가 같이 존재하는 경우 가장 높은 진단능을 보였다(area under the ROC curve = 0.702[95% 신뢰구간: 0.599-0.806], p < 0.001). 결론 자기공명영상에서 확인한 영상 소견을 바탕으로 인지기능 저하의 진단능을 평가하였다. 인지기능 저하의 진단에 있어서 엽미세출혈과 뇌실주위 뇌백질 신호강도 증가가 같이 존재하는 경우에 높은 진단능을 보였으며, 이러한 소견을 바탕으로 인지기능 저하를 진단하는 데 있어 영상 소견이 도움을 줄 수 있을 것이라는 가능성을 보여주었다.

• 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.

• 동의생리병리학회지
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• 제34권2호
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• pp.81-87
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• 2020

Cognitive impairment is symptoms of dementia, a degenerative brain disease that is drawing attention in a rapidly aging society. This study was conducted to investigate the improvement of cognitive function of Leonurus japonicus on scopolamine-induced memory impairment in mice and the effect and mechanism of memory recovery. In vivo studies were conducted on mice orally pretreated with L. japonicus in doses of 50, 100 and 200 mg/kg (p.o.) and scopolamine (1 mg/kg, i.p.) were injected 30 min before the behavioral task. Antioxidant activity was assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and acetylcholinesterase (AChE) inhibition activity evaluated by Ellman's method. In behavior studies showed that L. japonicus has an improved the memory of scopolamine-treated mice in Y-maze, passive avoidance and Morris water maze test. In addition, L. japonicus was also exerted free radical scavenging activity and inhibited acetyl cholinesterase activity. These results suggest that L. japonicus improves short-term and long-term memory in scopolamine-induced memory decline model and prevents scopolamine-induced memory impairments through in reduced oxidative stress and acetyl cholinesterase inhibition effect. Thus, L. japonicus is related to functional medicinal materials for prevention and treatment of human dementia patients.

• 생물정신의학
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• 제9권2호
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• pp.103-111
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• 2002

Neurocognitive research focusing on cognitive deficits in Depression has resulted in several important but yet potentially contradictory findings. Much literature documents the presence of significant neurocognitive impairments in depressive patients. Studies have shown that dysthymic disorder patients demonstrate a diffuse pattern of cognitive impairment which is frequently indistinguishable from that of focal braindamaged patients. Some reports have suggested that there is a focal pattern of deficit, such as anterior cingulate dysfunction, frontal lobe impairment, or dysfunction of the temporal-limbic cortex. The aim of this study is to evaluate the neurocognitive functions in dysthymic disorder patients, and to compare the functions with those of major depressive disorder patients. The subjects are 17 dysthymic disorder patients. And their neurocognitive functions are compared with those of 23 major depressive episode patients. Patients with a history of neurologic disease, alcohol dependence, substance abuse and mental retardation are excluded. They are assessed with a part of Vienna Test System which is computerized neurocognitive function tests and can evaluate attention, eductive ability, reproductive ability, visuoperceptual analysis, vigilance, visual immediate memory, the speed of information-processing, judgement, and fine motor coordinations. There are no other specific difference between two groups, except the result of cognitrone test. This study provides information about the neurocognitive functions and some difference between major depressive disorder patients and carefully diagnosed dysthymic disorder patients.

• 한국약용작물학회지
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• 제22권1호
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• pp.46-52
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• 2014

In traditional Korean and Chinese medicine, safflower (Carthamus tinctorius L.) for the treatment of central nervous system-related symptoms such as tremor, seizure, stroke and epilepsy. We investigated the effects of safflower could influence cerebral ischemia-induced neuronal and cognitive impairments. Administration of safflower for 1 day (200 mg/kg body weight, p.o.) increased the survival of hippocampal CA1 pyramidal neurons after transient global brain ischemia. And neurological functions measured as short term memory. Post-treatment with safflower for 2 times decreased the induction/reduction - induced production of neuronal cell loss from global cerebral ischemia. Safflower markedly decreased neuronal cell death and also caused a decrease in the content of thiobarbituric acid-reacting substances (TBARS) ($55.2{\pm}9.4{\mu}mol\;mg^{-1}$) and significant improvement of activities of glutathione (GSH) ($27.2{\pm}5.0{\mu}mol\;mg^{-1}$) in hippocampus. We conclude that treatment with safflower attenuated learning and memory deficits, and neuronal cell loss induced by global cerebral ischemia. These results suggest that safflower may be a potential candidate for the treatment of vascular dementia.

• Journal of Ginseng Research
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• 제41권2호
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• pp.201-208
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• 2017

Background: Panax vietnamensis Ha et Grushv. or Vietnamese ginseng (VG) is a recently discovered ginseng species. Studies on its chemical constituents have shown that VG is remarkably rich in ginseng saponins, particularly ocotillol saponins. However, the psychopharmacological effects of VG have not been characterized. Thus, in the present study we screened the psychopharmacological activities of VG in mice. Methods: VG extract (VGE) was orally administered to mice at various dosages to evaluate its psychomotor (open-field and rota-rod tests), sedative-hypnotic (pentobarbital-induced sleeping test), anti-stress (cold swimming test), anxiolytic (elevated plus-maze test), and cognitive (Y-maze and passive-avoidance tests) effects. Results: VGE treatment increased the spontaneous locomotor activity, enhanced the endurance to stress, reduced the anxiety-like behavior, and ameliorated the scopolamine-induced memory impairments in mice. In addition, VGE treatment did not alter the motor balance and coordination of mice and did not potentiate pentobarbital-induced sleep, indicating that VGE has no sedative-hypnotic effects. The effects of VGE were comparable to those of the Korean Red Ginseng extract. Conclusion: VG, like other ginseng products, has significant and potentially useful psychopharmacological effects. This includes, but is not limited to, psychomotor stimulation, anxiolytic, antistress, and memory enhancing effects.

• Animal cells and systems
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• 제16권4호
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• pp.302-312
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• 2012

The purpose of this study was to examine whether Phellodendri Cortex extract (PCE) could improve learning and memory impairments caused by lipopolysaccharide (LPS)-induced inflammation in the rat brain. The effect of PCE on modulating pro-inflammatory mediators in the hippocampus and its underlying mechanism were investigated. Injection of LPS into the lateral ventricle caused acute regional inflammation and subsequent deficits in spatial learning ability in the rats. Daily administration of PCE (50, 100, and 200 mg/kg, i.p.) for 21 days markedly improved the LPS-induced learning and memory disabilities in the Morris water maze and passive avoidance test. PCE administration significantly decreased the expression of pro-inflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and cyclooxygenase-2 mRNA in the hippocampus, as assessed by RT-PCR analysis and immunohistochemistry. Together, these findings suggest that PCE significantly attenuated LPS-induced spatial cognitive impairment through inhibiting the expression of pro-inflammatory mediators in the rat brain. These results suggested that PCE may be effective in preventing or slowing the development of neurological disorders, including Alzheimer's disease, by improving cognitive and memory function because of its anti-inflammation activity in the brain.

• 한국약용작물학회지
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• 제25권6호
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• pp.353-360
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• 2017

Background: A critical features of Alzheimer's disease (AD) is cognitive dysfunction, which partly arises from decreased in acetylcholine levels. AD afftected brains are characterized by extensive oxidative stress, which is thought to be primarily induced by the amyloid beta ($A{\beta}$) peptide. In a previous study, Cinnamomum loureiroi tincture inhibited acetylcholinesterase (AchE) activity. That study identified AChE inhibitor in the C. loureiroi extract. Furthermore, the C. loureiroi extract enhanced memory in a trimethyltin (TMT)-induced model of cognitive dysfunction, as assessed via two behavioral tests. Rosa laevigata extract protected against oxidative stress-induced cytotoxicity. Administrating R. laevigata extracts to mice significantly reversed $A{\beta}$-induced learning and memory impairment, as shown in behavioral tests. Methods and Results: We conducted behavioral to examine the synergistic effects of C. loureiroi and R. laevigata extracts in inhibiting AChE and counteracting TMT-induced learning and memory losses. We also performed biochemical assays. The biochemical results showed a relationship between increased oxidative stress and cholinergic neurons damage in TMT-treated mice. Conclusions: A diet containing C. loureiroi and R. laevigata extracts ameliorated learning and memory impairments in the Y-maze and passive avoidance tests, and exerted synergistic inhibitory effect against AChE and lipid peroxidation.

• Clinical and Experimental Pediatrics
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• 제64권7호
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• pp.313-321
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• 2021

Here we describe the neurodevelopmental outcomes of very low birth weight (VLBW) infants (birth weight ≤1,500 g) at 3 years of age in the Neonatal Research Network of Japan (NRNJ) database in the past decade and review the methodological issues identified in follow-up studies. The follow-up protocol for children at 3 years of chronological age in the NRNJ consists of physical and comprehensive neurodevelopmental assessments in each participating center. Neurodevelopmental impairment (NDI)-moderate to severe neurological disability-is defined as cerebral palsy (CP) with a Gross Motor Function Classification System score ≥2, visual impairment such as uni- or bilateral blindness, hearing impairment requiring hearing amplification, or cognitive impairment with a developmental quotient (DQ) of Kyoto Scale of Psychological Development score <70 or judgment as delayed by pediatricians. We used death or NDI as an unfavorable outcome in all study subjects and NDI in survivors using number of assessed infants as the denominator. Follow-up data were collected from 49% of survivors in the database. Infants with follow-up data had lower birth weights and were of younger gestational age than those without follow-up data. Mortality rates of 40,728 VLBW infants born between 2003 and 2012 were 8.2% before discharge and 0.7% after discharge. The impairment rates in the assessed infants were 7.1% for CP, 1.8% for blindness, 0.9% for hearing impairment, 15.9% for a DQ <70, and 19.1% for NDI. The mortality or NDI rate in all study subjects, including infants without follow-up data, was 17.4%, while that in the subjects with outcome data was 32.5%. The NRNJ follow-up study results suggested that children born with a VLBW remained at high risk of NDI in early childhood. It is important to establish a network follow-up protocol and complete assessments with fewer dropouts to enable clarification of the outcomes of registered infants.