• Biomolecules & Therapeutics
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• 제22권1호
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• pp.17-26
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• 2014

${\alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${\alpha}$-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of ${\alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${\alpha}$-Asarone significantly reduced TNF-${\alpha}$ and IL-$1{\beta}$ mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of ${\alpha}$-asarone treatment. ${\alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${\alpha}$-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of ${\alpha}$-asarone treatment. In the Morris water maze test, ${\alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${\alpha}$-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by ${\alpha}$-asarone may be one of the mechanisms for the ${\alpha}$-asarone-mediated ameliorating effect on memory deficits.

• 인지과학
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• 제11권3_4호
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• pp.33-43
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• 2000

정보처리 이론은 기억을 단기기억과 장기기억으로 구분하였다. 기억체계 이론은 기억이 정보처리 이론에서 가정하는 하나의 장기기억이 아닌 중다기억 체계로 기억이 조직화되어 lT다고 주장한다. 대표적인 기억체계정보처리 이론은 기억을 단기기억과 장기기억으로 구분하였다. 기억체계 이론은 기억이 정보처리 이론에서 가정하는 하나의 장기기억이 아닌 중다기억 체계로 기억이 조직화되어 lT다고 주장한다. 대표적인 기억체계 이론으로는 Schacter와 Tulving 의 기억모형(1994)과 Squire 의 장기기억 분류 모형(1987)이 있다 두 모형은 단기기억과 장기기억의 구분, 기억장애에 보존된 암묵기억 수행에는 견해가 일치하지만, 기억장애가 일화기억만의 손상인지 아니면 의미기억을 포함하는지는 견해가 다르다. 그러나 현재의 자료로서는 일화기억과 의미기억의 구분이 더 정확한 설명인가 아니면 서술기억과 비서술기억의 구분이 더 나은 설명인가는 분명하지 않다. 전두엽에 대한 더 자세한 연구가 일화기억과 의미기억의구분과 관련되어 있다. 이론으로는 Schacter와 Tulving 의 기억모형(1994)과 Squire 의 장기기억 분류 모형(1987)이 있다 두 모형은 단기기억과 장기기억의 구분, 기억장애에 보존된 암묵기억 수행에는 견해가 일치하지만, 기억장애가 일화기억만의 손상인지 아니면 의미기억을 포함하는지는 견해가 다르다. 그러나 현재의 자료로서는 일화기억과 의미기억의 구분이 더 정확한 설명인가 아니면 서술기억과 비서술기억의 구분이 더 나은 설명인가는 분명하지 않다. 전두엽에 대한 더 자세한 연구가 일화기억과 의미기억의구분과 관련되어 있다.

• 생물정신의학
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• 제17권2호
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• pp.70-78
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• 2010

Objectives : This study investigated the differences of working memory among the subtypes of ADHD. Methods : Eighty-one children and adolescents with ADHD and thirty normal controls were recruited. Children with any cognitive disorders and low intelligence were excluded. In order to evaluate the verbal and visuospatial working memory, Digit span and Finger windows tasks were measured, respectively. Performances on these measures between children with ADHD and controls were compared. Further, performances among the groups of ADHD predominantly inattentive(ADHD-IA)(n=40), predominantly hyperactive-impulsive(ADHD-HI)(n= 10), and combined type(ADHD-C)(n=31), were compared. Results : Scores of Finger windows forward task were lower in the ADHD group as compared to the control group, whereas, the Digit span forward showed no difference. Both scores of Digit span backward and Finger windows backward task were lower in the ADHD group than the controls. Children with ADHD-IA performed poorer than children with ADHD-C on the Finger windows backward task. Conclusion : The results of this study showed that children with ADHD have deficits in spatial short-term memory and verbal and visuospatial working memory when compared to normal children. The deficits were evident in children with ADHD-IA subtype and in particular, performance on the visuospatial working memory task in this group was poorer than the ADHD-C group.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.304.3-305
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• 2002

The present study investigated the passive avoidance and spatial learning in the ${\mu}$-opioid receptor gene knockout mice and wild type mice. In the step-through passive avoidance task. the ${\mu}$-opioid receptor knockout mice did not differ from the wild type mice. In Morris water maze. however. the ${\mu}$-opioid receptor knockout mice showed significant memory deficit compared to wild type mice. (omitted)

• BMB Reports
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• 제42권5호
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• pp.239-244
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• 2009

New neurons are continually generated in the subgranular zone of the dentate gyrus and in the subventricular zone of the lateral ventricles of the adult brain. These neurons proliferate, differentiate, and become integrated into neuronal circuits, but how they are involved in brain function remains unknown. A deficit of adult hippocampal neurogenesis leads to defective spatial learning and memory, and the hippocampi in neuropsychiatric diseases show altered neurogenic patterns. Adult hippocampal neurogenesis is not only affected by external stimuli but also regulated by internal growth factors including BDNF, VEGF and IGF-1. These factors are implicated in a broad spectrum of pathophysiological changes in the human brain. Elucidation of the roles of such neurotropic factors should provide insight into how adult hippocampal neurogenesis is related to psychiatric disease and synaptic plasticity.

• 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.

• 대한본초학회지
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• 제35권5호
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• pp.33-39
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• 2020

Objectives : Increasing evidence supports the biological and pharmacological activities of essential oils on the central nervous system such as pain, anxiety, attention, arousal, relaxation, sedation and learning and memory. The purpose of present work is to investigate the protective effect and molecular mechanism of cypress essential oil (CEO) against scopolamine (SCO)-induced cognitive impairments in C57BL/6 mice. Methods : A series of behavior tests such as Morris water maze, passive avoidance, and fear conditioning tests were conducted to monitor learning and memory functions. Immunoblotting and RT-PCR were also performed in the hippocampal tissue to determine the underlying mechanism of CEO. Results : SCO induced cognitive impairments as assessed by decreased step-through latency in passive avoidance test, relatively low freezing time in fear conditioning test, and increased time spent to find the hidden platform in Morris water maze test. Conversely, CEO inhalation significantly reversed the SCO-induced cognitive impairments in C57BL/6 mice comparable to control levels. To elucidate the molecular mechanisms of memory enhancing effect of CEO we have examined the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. CEO effectively elevated the protein as well as mRNA expression of BDNF via activation of cAMP response element binding protein (CREB). Conclusions : Our findings suggest that CEO inhalation effectively restored the SCO-impaired cognitive functions in C56BL/6 mice. This learning and memory enhancing effect of CEO was partly mediated by up-regulation of BDNF via activation of CREB.

• Anatomy and Cell Biology
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• 제56권4호
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• pp.494-507
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• 2023

Vascular dementia (VaD) is characterized by progressive memory impairment, which is associated with microglia-mediated neuroinflammation. Polyphenol-rich natural plants, which possess anti-inflammatory activities, have attracted scientific interest worldwide. This study investigated whether Rubus fruticosus leaf extract (RFLE) can attenuate VaD. Sprague-Dawley rats were separated into five groups: SO, sham-operated and treated with vehicle; OP, operated and treated with vehicle; RFLE-L, operated and treated with low dose (30 mg/kg) of RFLE; RFLE-M, operated and treated with medium dose (60 mg/kg) of RFLE; and RFLE-H, operated and treated with high dose (90 mg/kg) of RFLE. Bilateral common carotid artery and hypotension were used as a modeling procedure, and the RFLE were intraorally administered for 5 days (preoperative 2 and postoperative 3 days). The rats then underwent memory tests including the novel object recognition, Y-maze, Barnes maze, and passive avoidance tests, and neuronal viability and neuroinflammation were quantified in their hippocampi. The results showed that the OP group exhibited VaD-associated memory deficits, neuronal death, and microglial activation in hippocampi, while the RFLE-treated groups showed significant attenuation in all above parameters. Next, using BV-2 microglial cells challenged with lipopolysaccharide (LPS), we evaluated the effects of RFLE in dynamics of proinflammatory mediators and the upstream signaling pathway. RFLE pretreatment significantly inhibited the LPS-induced release of nitric oxide, TNF-α, and IL-6 and upregulation of the MAPKs/NF-κB/iNOS pathway. Collectively, we suggest that RFLE can attenuate the histologic alterations and memory deficits accompanied by VaD, and these roles are, partly due to the attenuation of microglial activation.

• 구강회복응용과학지
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• 제23권2호
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• pp.179-186
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• 2007

The decrease of masticatory function caused by tooth loss leads to a decrease of cerebral blood flow volume resulting in impairment of cognitive function and learning memory disorder. However, the reduced mastication-mediated morphological alteration in the central nervous system (CNS) responsible for senile deficit of cognition, learning and memory has not been well documented. In this study, the effect of the loss of the molar teeth (molarless condition) on the hippocampal expression of glial fibrillary acidic protein (GFAP) protein was studied by immunohistochemical techniques. The results were as follows : 1. The molarless mice showed a lower density of pyramidal cells in the cornu ammonis 1 (CA1) and dentate gyrus (DG) region of the hippocampus than control mice. 2. Immunohistochemical analysis showed that the molarless condition enhanced the time-dependent increase in the cell density and hypertrophy of GFAP immunoreactivity in the CA1 region of the hippocampus. The molarless condition enhanced an time-dependent decrease in the number of neurons in the hippocampal formation and the time-dependent increase in the number and hypertrophy of GFAP-labeled cells in the same region. The data suggest a possible link between reduced mastication and histological changes in hippocampal formation that may be one risk factor for senile impairment of cognitive function and spatial learning memory.

• 혜화의학회지
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• 제12권1호
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• pp.11-26
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• 2003

Alzheimer's disease (AD) is characterized by amyloid deposition and associated loss of neunons in brain regions involved in learning and memory processes. Several causes of evidence support that the congnitive disturbance is closed associated with the deficit of cerebral acetylcholine neurotransmission, and the effect of carboxyl terminal 105 amino acid fragment (CT105) of the amyloid precursor protein (APP) on the gene expression of proinflammatory cytokines. We tested it on the scopolamine-induced amnesia model of the ICR mouse using the Morris water maze with repeated orally administration of 1st Green-Tea extract (200 mg/kg) and 2nd Green-Tea extract (200 mg/kg). The Green-Tea prevents impairment of learning and memory and neuronal loss in mouse models of cognitive disturbance and it demonstrated selectivity for inhibition of acetylcholinesterase (AChE). Furthermore, the repeated administration of Green-Tea, CT105-induced alzheimer's mouse model showed central cholinergic activity by ameliorates learning and memory impairment, and isolation of CD14 microglia showed significantly decreases intracellular release of the proinflammatory cytokines tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$ and reactive oxygen species (ROS). Because of its composite profile, oral therapeutic index and a prophylactic, Green-Tea is considered the better therapeutic candidate for the treatment of Alzheimer's disease.