• The Korean Journal of Pain
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• 제35권3호
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• pp.261-270
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• 2022

Background: The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus's effects on capsaicin-induced pulpal nociception and cognitive impairments in rats. Methods: Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. Results: Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 µL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 µL/rat) suppressed orexin's effects. Conclusions: Orexin-A signaling in the RVM and hippocampus modulates capsaicin-induced pulpal nociception in male rats by increasing BDNF expression and decreasing COX-2 expression.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.27-37
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• 2020

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

• 동의생리병리학회지
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• 제25권1호
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• pp.37-47
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• 2011

This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.

• BMB Reports
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• 제46권2호
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• pp.103-106
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• 2013

Phosphoinositide 3-kinases (PI3Ks) play key roles in synaptic plasticity and cognitive functions in the brain. We recently found that genetic deletion of $PI3K{\gamma}$, the only known member of class IB PI3Ks, results in impaired N-methyl-D-aspartate receptor-dependent long-term depression (NMDAR-LTD) in the hippocampus. The activity of RalA, a small GTP-binding protein, increases following NMDAR-LTD inducing stimuli, and this increase in RalA activity is essential for inducing NMDAR-LTD. We found that RalA activity increased significantly in $PI3K{\gamma}$ knockout mice. Furthermore, NMDAR-LTD-inducing stimuli did not increase RalA activity in $PI3K{\gamma}$ knockout mice. These results suggest that constitutively increased RalA activity occludes further increases in RalA activity during induction of LTD, causing impaired NMDAR-LTD. We propose that $PI3K{\gamma}$ regulates the activity of RalA, which is one of the molecular mechanisms inducing NMDAR-dependent LTD.

• 공업화학
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• 제17권3호
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• pp.260-266
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• 2006

메모리 기능의 미세 셀 폴리우레탄 폼용 옥시에틸렌변성실록산 계면활성제의 합성을 위해 폴리메틸하이드로겐실록산(D = 75, D' = 15)의 수소작용기에 수소규소화반응을 이용하여 다양한 폴리알킬렌옥사이드를 치환하여 합성하였다. 폴리알킬렌 옥사이드는 에틸렌옥사이드(EO) 또는 EO와 프로필렌옥사이드(PO)의 혼합성분이 반복되는 구조에 말단기는 메틸 또는 하이드록실기를 갖는 물질들을 이용하였다. NMR과 GPC 분석을 이용하여 분자 구조와 분자량 변화를 통하여 합성반응의 진행 여부 및 생성물 수율(98%)을 파악하였다. EO 12 반복단위로 합성된 계면활성제의 첨가량을 0.6~2.0 part per hundred polyol (pphp)까지 증가시켜 메모리 기능의 우레탄 폼 발포에 적용하여 폼의 물리적 특성을 측정한 결과 셀 사이즈(최소 $0.868{\mu}m$), 공기유량(air flow, -78 KPa), 복원시간(recovery time, 8 sec) 등의 결과를 나타내었다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2003년도 생물공학의 동향(XII)
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• pp.630-633
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• 2003

Transfer of an electron from one site to another in a molecular or between molecules and/or electrodes is one of the most fundamental and ubiquitous processes in chemistry, biology and physics. In this study fusion proteins composed by green fluorescent protein(GFP) and cytochrome b562 were used in fabricating molecular array as an electron sensitizer and electron acceptor, Protein formation onto the substrate was performed by the self-assembly technique. The fusion protein film were analyzed using scanning probe microscope(SPM), Surface Plasmon Resornance(SPR) and hybrid STM/I-V. The results suggest that the proposed molecular photodiode can be used as a basic unit of the memory device.

• Molecules and Cells
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• 제47권1호
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• pp.100006.1-100006.10
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• 2024

Nitric oxide (NO) serves as an evolutionarily conserved signaling molecule that plays an important role in a wide variety of cellular processes. Extensive studies in Drosophila melanogaster have revealed that NO signaling is required for development, physiology, and stress responses in many different types of cells. In neuronal cells, multiple NO signaling pathways appear to operate in different combinations to regulate learning and memory formation, synaptic transmission, selective synaptic connections, axon degeneration, and axon regrowth. During organ development, elevated NO signaling suppresses cell cycle progression, whereas downregulated NO leads to an increase in larval body size via modulation of hormone signaling. The most striking feature of the Drosophila NO synthase is that various stressors, such as neuropeptides, aberrant proteins, hypoxia, bacterial infection, and mechanical injury, can activate Drosophila NO synthase, initially regulating cellular physiology to enable cells to survive. However, under severe stress or pathophysiological conditions, high levels of NO promote regulated cell death and the development of neurodegenerative diseases. In this review, I highlight and discuss the current understanding of molecular mechanisms by which NO signaling regulates distinct cellular functions and behaviors.

• Journal of Ginseng Research
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• 제45권5호
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• pp.599-609
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• 2021

Ginseng has long been considered as an herbal medicine. Recent data suggest that ginseng has antiinflammatory properties and can improve learning- and memory-related function in the central nervous system (CNS) following the development of CNS neuroinflammatory diseases such as Alzheimer's disease, cerebral ischemia, and other neurological disorders. In this review, we discuss the role of ginseng in the neurovascular unit, which is composed of endothelial cells surrounded by astrocytes, pericytes, microglia, neural stem cells, oligodendrocytes, and neurons, especially their blood-brain barrier maintenance, anti-inflammatory effects and regenerative functions. In addition, cell-cell communication enhanced by ginseng may be attributed to regeneration via induction of neurogenesis and angiogenesis in CNS diseases. Thus, ginseng may have therapeutic potential to exert cognitive improvement in neuroinflammatory diseases such as stroke, traumatic brain injury, multiple sclerosis, Parkinson's disease, and Alzheimer's disease.

• 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.

• Molecules and Cells
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• 제39권8호
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• pp.603-610
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• 2016

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.