• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.515-522
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• 2015

Notch signaling is a key regulator of neuronal fate during embryonic development, but its function in the adult brain is still largely unknown. Mind bomb-2 (Mib2) is an essential positive regulator of the Notch pathway, which acts in the Notch signal-sending cells. Therefore, genetic deletion of Mib2 in the mouse brain might help understand Notch signaling-mediated cell-cell interactions between neurons and their physiological function. Here we show that deletion of Mib2 in the mouse brain results in impaired hippocampal spatial memory and contextual fear memory. Accordingly, we found impaired hippocampal synaptic plasticity in Mib2 knock-out (KO) mice; however, basal synaptic transmission did not change at the Schaffer collateral-CA1 synapses. Using western blot analysis, we found that the level of cleaved Notch1 was lower in Mib2 KO mice than in wild type (WT) littermates after mild foot shock. Taken together, these data suggest that Mib2 plays a critical role in synaptic plasticity and spatial memory through the Notch signaling pathway.

• The Journal of Korean Medicine
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• v.31 no.5
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• pp.167-178
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• 2010

Objectives: The present study investigated the effects of acupuncture treatment and their mechanism by using the kainic acid (KA)-induced epilepsy mouse model. Materials and Methods: The seizure was induced by an intraperitoneal (i.p.) injection of 30 mg/kg KA, and the acupuncture treatment was subsequently administered to acupoint Shaofu(HT8) bilaterally with two pretreatment sessions before injection (total 3 times over 3 days). Twenty four hours after injection, we observed the survival of neuronal cells in the CA3 region of the hippocampus. In addition, the activation of microglia and astrocytes was observed by using CD11b and GFAP immunohistochemistry in the same region. Results: The results indicate that acupuncture treatment reduced the rate of neural cell death in the CA3 region of the hippocampus and decreased the activations of microglia and astrocytes in this region. Conclusion: These results demonstrate that acupuncture treatment protects hippocampal neuronal cell death from KA-induced epileptic seizure by inhibiting the activations of microglia and astrocytes.

• Natural Product Sciences
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• v.16 no.2
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• pp.99-106
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• 2010

This experiment was undertaken to investigate whether methanol extract of fruit peel of Dimocarpus longan Lour. (MEFL) protects against kainic acid (KA)-induced seizure. Oral administration of MEFL (1, 2 and 4 mg/kg) increased KA (50 mg/kg)-induced survival rate and latency of convulsion onset, and deceased seizure scores and weight loss induced by intraperitoneal (i.p) injection of KA in mice. In addition, MEFL protected against cell death in the hippocampus of rat brain after KA-administration as analyzed by using TUNEL assay in rats. MEFL also significantly blocked seizure-form of electroencephalogram (EEG) power spectra induced by KA in rats. MEFL also inhibited elevation of [$Ca^{2+}$]i and increased [$Cl^-$]i induced by KA in cultured neuronal cells. Therefore, it is suggested that MEFL protects against seizure induced by KA, decreasing [$Ca^{2+}$]i.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.2
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• pp.434-440
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• 2005

This study was conducted to find out the effect of Bojungikgitanggamibang(BIT) on growth, learning and memory of rats. The effects of BIT on learning and memory performance were examined in normal or memory impaired mice by using water maze task. Memory was impaired by 192 saporin. Body weight and growth of bone and tail of sample group were not significant compared with those of control groups. Acquisition test of water maze revealed that acqusitive ability of sample group significantly improved on 4,5th day compared with control group, while retentive ability of sample group was not significant. ChAT cell numbers of medial septum of sample group was significant compared with control group, and so was those of CA1, CA2 parts of hippocampus. On ChAT cell numbers of hippocampus, in CA2 part. These results suggest that BIT has an improving effect on the impaired learning through the effects on memory registration and retrieval.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.309-318
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• 2024

Compared to other organs, the brain has limited antioxidant defenses. In particular, the hippocampus is the central region for learning and memory and is highly susceptible to oxidative stress. Glial cells are the most abundant cells in the brain, and sustained glial cell activation is critical to the neuroinflammation that aggravates neuropathology and neurotoxicity. Therefore, regulating glial cell activation is a promising neurotherapeutic treatment. Quinic acid (QA) and its derivatives possess anti-oxidant and anti-inflammatory properties. Although previous studies have evidenced QA's benefit on the brain, in vivo and in vitro analyses of its anti-oxidant and anti-inflammatory properties in glial cells have yet to be established. This study investigated QA's rescue effect in lipopolysaccharide (LPS)-induced behavior impairment. Orally administering QA restored social impairment and LPS-induced spatial and fear memory. In addition, QA inhibited proinflammatory mediator, oxidative stress marker, and mitogen-activated protein kinase (MAPK) activation in the LPS-injected hippocampus. QA inhibited nitrite release and extracellular signal-regulated kinase (ERK) phosphorylation in LPS-stimulated astrocytes. Collectively, QA restored impaired neuroinflammation-induced behavior by regulating proinflammatory mediator and ERK activation in astrocytes, demonstrating its potential as a therapeutic agent for neuroinflammation-induced brain disease treatments.

• Journal of Acupuncture Research
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• v.18 no.6
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• pp.206-214
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• 2001

The purpose of this study was to determine the effects of Puerariae flos herb-acupuncture on hippocampal neural cell proliferation. Sprague-Dawley rats were randomly assigned into 4 groups; control group, control with herb-acupuncture group, alcohol group, alcohol with herb-acupuncture group group. Control groups were received with NaCl, while alcohol intoxication groups were injected intraperitoneally with alcohol (2 g/㎏) twice per day for 3 days. Herb-acupuncture groups were injected on Zhongwan (CV 12) for 5 consecutive days. Bromo-deoxyuridine (BrdU) was injected into all animal per day for 5 days. For the detection of BrdU-positive cells in dentate gyrus of hippocampus, immunohistochemistry was performed. In alcohol group, a significant decrease in BrdU-positive cells was observed compared to control group. In alcohol with herb-acupuncture group, BruU-positive cells increased significantly compared to alcohol group. In conclusion, the present results revealed that new cell proliferation is enhanced in the dentate gyros of young Sprague-Dawley rats through Puerariae flos herb-acpuncuture in an acute alcoholic intoxication condition.

• Toxicological Research
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• v.12 no.2
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• pp.203-211
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• 1996

Methanol has been widely used as an industrial solvent and environmental exposure to methanol would be expected to be increasing. In humans, methanol causes metabolic acidosis and damage to ocular system, and can lead to death in severe and untreated case. Clinical symptoms are attributed to accumulation of forrnic acid which is a metabolic product of methanol. In humans and primates, formic acid is accumulated after methanol intake but not in rodents due to the rapid metabolism of methanol. Neverthless, the developmental and reproductive toxicity were reported in rodents. Previous reports showed that perinatal exposure to ethanol produces a variety of damage in human central nervous system by direct neurotoxicity. This suggests that the mechanism of toxic symptoms by methanol in rodents might mimic that of ethanol in human. In the present study I hypothesized that methanol can also induce toxicity in neuronal cells. For the study, primary culture of rat hippocampal neurons and glias were empolyed. Hippocampal cells were prepared from the embryonic day-17 fetuses and maintained up to 7 days. Effect of methanol (10, 100, 500 and 1000 mM) on neurite outgrowth and cell viability was investigated at 0, 18 and 24 hours following methanol treatment. To study the changes in proliferation of glial cells, protein content was measured at 7 days. Neuronal cell viability in culture was not altered during 0-24 hours after methanol treatment. 10 and 100 mM methanol treatment significantly enhanced neurite outgrowth between 18-24 hours. 7-day exposure to 10 or 100 mM methanol significantly increased protein contents but that to 1000 mM methanol decreased in culture. In conclusion, methanol may have a variety of effects on growing and differentiation of neurons and glial cells in hippocampus. Treatment with low concentration of methanol caused that neurite outgrowth was enhanced during 18-24 hours and the numbers of glial cell were increased for 7 days. High concentration of methanol brought about decreased protein contents. At present, the mechanism responsible for the methanol- induced enhancement of neurite outgrowth is not clear. Further studies are required to delineate the mechanism possibly by employing molecular biological techniques.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.4
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• pp.921-933
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• 2007

This experiment was designed to investigate the effects of the KBCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model Induced by ${\beta}A$. The effects of the KBCMT hot water extract on expression of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NOS-II, COX-2 mRNA and production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NO in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the KBCMT hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, CD68 and CD11b; (3) AChE in serum (4) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The KBCMT hot water extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in BV2 microglia cell line treated with LPS. The KBCMT hot water extract suppressed the production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, NO in BV2 microglial cell line treated with LPS. The KBCMT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured stop-through latency and distance movemet-through latency The KBCMT ultra-fine powder suppressed the expression of TNF-a protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder decreased AChE significantly in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The KBCMT hot water extract & ultra-fine powder reduced the tau protein, GFAP, and presenilin1, 2 of hippocampus in the mice with Alzheimer's disease induced by ${\beta}A$. These results suggest that the KBCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the KBCMT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.688-699
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• 2007

This experiment was designed to investigate the effect of the SST hot water extract & ultra-fine Powder on Alzheimer's Disease Model Induced by ${\beta}$A. The effects of the SST hot water extract on expression of IL-1${\beta}$, IL-6, TNF-${\alpha}$, NOS-II, COX-2 mRNA and production of IL-l${\beta}$, IL-6, TNF-${\alpha}$, NO in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the SST hot water extract & ultra-fine powder on (1) the behavior (2) expression of IL-1${\beta}$, TNF-${\alpha}$, MDA, (3) Glucose, AChE in serum (4) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. The SST hot water extract suppressed the expression of IL-1${\beta}$, IL-6 and TNF-a mRNA ${\alpha}$in BV2 microglia cell line treated with LPS. The SST hot water extract suppressed the production of IL-1${\beta}$, IL-6, TNF-${\alpha}$, NO in BV2 microglial cell line treated with LPS. The SST hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}$A in the Morris water maze experiment, which measured stop-through latency. The SST ultra-fine powder suppressed the expression of TNF-a protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder decreased AChE significantly in the serum of the mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder reduced infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. The SST hot water extract & ultra-fine powder reduced the tau protein, GFAP, and presenilin1, 2 of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. These results suggest that the SST hot water extract & ultra-fine powder may be effective for the prevention and treatment of A1zheimer's disease. Investigation into the clinical use of the SST hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• BMB Reports
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• v.35 no.1
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• pp.87-93
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• 2002

Neural cell survival is an essential concern in the aging brain and many diseases of the central nervous system. Neural transplantation of the stem cells are already applied to clinical trials for many degenerative neurological diseases, including Huntington's disease, Parkinson's disease, and strokes. A critical problem of the neural transplantation is how to reduce their apoptosis and improve cell survival. Neurotrophic factors generally contribute as extrinsic cues to promote cell survival of specific neurons in the developing mammalian brains, but the survival factor for neural stem cell is poorly defined. To understand the mechanism controlling stem cell death and improve cell survival of the transplanted stem cells, we investigated the effect of plausible neurotrophic factors on stem cell survival. The neural stem cell, HiB5, when treated with PDGF prior to transplantation, survived better than cells without PDGF. The resulting survival rate was two fold for four weeks and up to three fold for twelve weeks. When transplanted into dorsal hippocampus, they migrated along hippocampal alveus and integrated into pyramidal cell layers and dentate granule cell layers in an inside out sequence, which is perhaps the endogenous pathway that is similar to that in embryonic neurogenesis. Promotion of the long term-survival and differentiation of the transplanted neural precursors by PDGF may facilitate regeneration in the aging adult brain and probably in the injury sites of the brain.