• Journal of Korean Neurosurgical Society
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• v.29 no.11
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• pp.1429-1436
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• 2000

Objectives : This study was performed in cultured rat hippocampal neurons to investigate the acute electrophysiological features of ionotropic glutamate receptors which act as a major excitatory neurotransmitter in mammalian brain. Method : Glutamate receptor agonists were applied into the bath solution embedding in whole-cell patch-clamp recording of single hippocampal neuron. Results : In voltage-clamped at -60mV and the presence of 1mmol $Mg^{2+}$, extracellulary applied NMDA did not induce any inward current. Both the elimination of $Mg^{2+}$ and addition of glycine in bath, however, elicited a NMDAinduced inward current. $Mg^{2+}$ block current was increased gradually in more negative potentials from -30mV, showing a negative slope in I-V plot with $Mg^{2+}$. Glutamate-induced current represented an outward rectification. A non-NMDA receptor component occupied about 40% of glutamate-induced current in the voltage range of -80mV to +60mV. Conclusion : Present study suggests that glutamate activates acutely the non-NMDA receptors which induces an inward current in the level of resting membrane potential. This makes the membrane potential increase and can activate the NMDA receptors that permit calcium influx against $Mg^{2+}$ block. At the depolarized state of neuron, there may be recovery mechanisms of membrane potential to repolarize irrespective of voltage-dependent potassium channels in the hippocampal neurons.

• Korean Journal of Biological Psychiatry
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• v.7 no.2
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• pp.164-173
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• 2000

This study was carried out to investigate the direct neurotoxicity of alcohol on CNS and the effects of piracetam or vitamins on ultrastructural changes of the rat cerebellar and hippocampal neurons during long-term alcohol treatment. To evaluate the results, quantitative analysis were done for light and electronic microscopic findings. On the light microscopy, red degeneration of pyramidal cells and Purkinje cells was found more apparently in the alcohol only treated group than in the control group. On the electron microscopy, increased lipofuscin pigments were found in cerebellum and hippocampus. In quantitative analysis, vitamins significantly reduced red degeneration in both hippocampus and cerebellum. However, piracetam significantly reduced red degeneration in cerebellum but not in hippocampus. Lipofuscin pigments in Purkinje cells and pyramidal cells were significantly reduced in the alcohol with piracetam treated group than the alcohol only treated group. However, vitamins had no significant reducing effect of lipofuscin pigments in Purkinje cells and pyramidal cells. According to the results, it is concluded that vitamins deficiency might cause red degeneration of pyramidal cell after long-term alcohol treatment, but increment of lipofuscin pigments in pyramidal and Purkinje cell may be caused by alcohol itself or its metabolite rather than vitamins deficiency. Piracetam seems to improve cognitive function impairment caused by alcohol consumption.

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.315-322
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• 2006

FS11052, a novel microbial metabolite from Streptomyces spp. was identified as a small molecular substance and shown inhibition activities for the release of neurotransmitter from rat hippocampal neuron and PC12 cells. FS11052 is an inhibitor of tritiated norepinephrine ($[^3H]-NE$) release in high $K^+$ buffer solution containing ionomycin, indicating that FS11052 inhibits neurotransmitter release after the influx of $Ca^{2+}$ ions. When examined the effect of FS11052 on glucuronidase release from guinea pig neutrophils, FS11052 inhibited glucuronidase release: when treated with $5{\mu}g/ml$ of FS11052, which was not induced cellular cytotoxicity. The fact that the glucuronidase release in neutrophil and norepinephrine release in neuron was inhibited suggests the similarity in the locations and the mechanisms of FS11052 action targets. When treated with $5{\mu}g/ml$ of FS11052, $[^3H]-NE$ release and neurite extension for both rat hippocampal neurons and PC12 cells were prevented. These observations of FS11052 functioning as an inhibitor of neurotransmitter release suggest that FS11052 has an important role in synaptic transmission in neuron.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.15 no.1
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• pp.91-100
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• 2004

Objectives：The effects of repeated maternal separation on the expression of glucocorticoid receptor (GR) and cyclooxygenase-2(COX-2) in the hippocampus of rat pups at preweanling stage were evaluated. Methods：The experimental, Repeated Maternal Separation group(N=4) was separated from the mother for four hours a day over a period of ten days beginning with postnatal day 4. The Control group(N=4), on the other hand, did not separated from the mother at all. GR and COX-2 expression in the hippocampus was examined by immunohistochemistry on postnatal day 14. Results：It was determined that the number of GR-immunopositive cells in the dentate gyrus of the hippocampus was significantly increased in the Repeated Maternal Separation group. The numbers of COX-2-immunopositive cells in the CA1 and CA3 were also significantly higher in the Repeated Maternal Separation group. Conclusion：These results suggest that maternal separation may be a significant developmental stress that induces GR and COX-2 expression in the hippocampus of developing pups.

• Journal of Life Science
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• v.26 no.12
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• pp.1458-1465
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• 2016

We investigated the neuroprotective effect of an ethanol extract from Asparagus cochinchinensis (AC) against glutamate-induced toxicity in the HT22 hippocampal cell, which is an ideal in vitro model for oxidative stress. The neuroprotective effects of AC in HT22 cells were evaluated by analyzing cell viability, lactate dehydrogenase (LDH), flow cytometry for cell death types, reactive oxygen species (ROS), mitochondria membrane potential (MMP), and Western blot assays. In the cell death analysis, AC treatment resulted in significantly attenuated glutamate-induced loss of cell viability with a decrease in LDH release. AC treatment also reduced glutamate-induced apoptotic cell death. In the ROS and MMP analysis, AC treatment inhibited the elevation of intracellular ROS induced by glutamate exposure and the disruption of MMP. In oxidative stress-related proteins analysis, AC treatment inhibited the expression of poly ADP ribose polymerase and heme oxygenase-1 by glutamate. These results indicate that AC exerts a significant neuroprotective effect against glutamate-induced hippocampal damage by decreasing ROS production and stabilizing MMP. Thus, AC potentially provides a new strategy for the treatment of oxidative stress-related diseases.

• Science of Emotion and Sensibility
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• v.14 no.3
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• pp.425-434
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• 2011

In the present study was to examine the influence of cold stress conditions on memory function in relation with 5-hydroxytryptamine(serotonin, 5-HT), trptophanhydroxylase(TPH) expression and cell proliferation in the hippocampus. For this study, male Sprague-Dawley rats weighing $250{\pm}10g$ (7 weeks in age) were used. The rats were randomly divided into three groups(n = 10 in each group): the $22^{\circ}C$-control group, the $4^{\circ}C$-3 days group, the $4^{\circ}C$-5 weeks group. The environmental temperature at $22^{\circ}C$ set as the normal conditions, $4^{\circ}C$ was as the cold stress conditions. The present results showed that cold stress conditions shorten latency, representing cold stress disturbed memory function. 5-HT and TPH expressions in the dorsal raphe were increased cold stress. Neurogenesis in the dentate gyrus was increased under cold conditions. The present study revealed that cold stress exerted deteriorative memory function. However, through increasing of 5-HT, TPH and BrdU expression under cold stress conditions did not show memory enhancing effect.

• Journal of Life Science
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• v.26 no.7
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• pp.812-818
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• 2016

The aim of this study was to investigate the anti-amnesic effect of Stachys sieboldii MIQ. according to the mixing ratio of calcium on scopolamine-induced learning and memory impairment, in vivo. At the end of the adaptation period, SD rats were divided into a normal group (N), a control group (C: scopolamine), a positive control group (PC: scopolamine + tacrine), and a sample group (S: scopolamine + Stachys sieboldii MIQ., 1CS: scopolamine + low calcium-mixed Stachys sieboldii MIQ., 5CS: scopolamine + high calcium-mixed Stachys sieboldii MIQ.), and were tested with learning and memory tests. The C and CS groups were found to have a decreased scopolamine-induced memory deficit in the Y-maze and water maze tests. Brain tissue analysis showed that the CS group decreased acetylcholinesterase (AChE) activity and increased acetylcholine (Ach) content, both of which are indicative of neuronal cell activity. From a light microscopy study, the nucleus of neurons in the hippocampus of the brain was more shrunken or condensed in the C group compared to the CS group. In the CS group, the damage to the neurons in the hippocampus of the brain was suppressed. These results suggest that Stachys sieboldii MIQ. according to the mixing ratio of calcium provides a significant anti-amnesic effect against scopolamine-induced cholinergic system deficits and cognitive impairment.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.29-44
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• 2010

Objectives : The purpose of this study was to investigate the effect of Gentianae Radix on neurogenesis and apoptosis in ethanol- induced newborn rats hippocampus dentate gyrus. Methods : In vivo, laboratory animals were divided into three groups; Normal group(N), Control group(C) and Treated group (TG)(n=7 for each group). N were treated saline daily for five days. C were treated 1.5 g/kg ethanol and saline daily for five days. TG were treated 1.5 g/kg ethanol and 300 mg/kg Gentianae Radix daily for five days. BrdU(5-bromo-2-deoxyuridine) assay was used to test neurogenesis in the dentate gyrus. And TUNEL(Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay was used to test apoptosis in the dentate gyrus. Three groups were measured body weight, serum ethanol concentration, BrdU-positive cells and TUNEL-positive cells in the dentate gyrus. In vitro, MTT(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to test viability in SK-N-MC cells. BrdU assay was used to test neurogenesis in SK-N-MC cells. DNA fragmentation and caspase-3 enzyme activity assay were used to test apoptosis in SK-N-MC cells. And treated ethanol and Gentianae Radix of all in vitro tests were made various concentration. Results : In vivo, Gentianae Radix modulated ethanol-induced neurogenesis and apoptosis in newborn rats hippocampus dentate gyrus. In vitro, TG 100 ${\mu}g/ml$ have significantly modulated ethanol-induced neurogenesis and apoptosis in SK-N-MC cells. And only TG 100 ${\mu}g/ml$ have significantly protected SK-N-MC cells from ethanol-induced cytotoxicity. Conclusions : Gentianae Radix may have the effect that modulated ethanol-induced neurogenesis and apoptosis in SK-N-MC cells.

• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.294-306
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• 1995

There has recently been increasing interest in the use of NMDA receptor antagonists as potential neuroprotective agents for the treatment of ischemic stroke. To evaluate the neuroprotective effect of the selective non-competitive NMDA receptor antagonist MK-801 in focal cerebral ischemia, local cerebral glucose utilization (ICGU) was examined in 15 neuroanatomically discrete regions of the conscious rat brain using the 2-deoxy-D[$^{14}C$] glucose quantitative autoradiographic technique 24 hr after left middle cerebral artery occlusion (MCAO). Animals received MK-801 (5 mg/kg i.v.) or saline vehicle before (20-30 min) or after (30 min) MCAO. Both pretreatment and posttreatment of MK-801 increased occluded/non-occluded ICGU ratio in 7 and 5 of the 15 regions measured, respectively (most notably in cortical structures). Following MK-801 pretreatment, there was evidence of widespread increases in ICGU not only in the non-occluded hemisphere (12 of the 15 areas studied) but also in the occluded hemisphere (13 of the 15 areas studied), while MK-801 postreatment did not significantly increase ICGU both in the normal and occluded hemispheres. These data indicate that MK-801 has a neuroprotective effect in focal cerebral ischemia and demonstrate that MK-801 provides widespread alterations of glucose utilization in conscious animals.

• Journal of Life Science
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• v.19 no.1
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• pp.21-33
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• 2009

In this study, we investigated the effect of Rhei Rhizoma (RR; 大黃) water extract on gene expression in a hypoxia model of cultured rat hippocampal neurons. RR water extract $(2.5{\mu}g/ml)$ was added to the culture media on day 10 in vitro (DIV10), and a hypoxic shock (2% $O_2$/5% $CO_2$, $37^{\circ}C$, 3 h) was given on DIV13. After maintaining the cultures in normoxia for 24 hr, total RNA was isolated and used for microarray analysis. The MA-plot indicated that most genes were up- or downregulated within 2-fold. There were more downregulated genes (725 ea) than upregulated ones (472 ea) when larger than Global M value 0.2 (i.e., >15% increase) or smaller than Global M value -0.2 (i.e., >15% decrease) were considered. Antiapoptosis genes such as Tegt (2.4-fold), Nfkb1 (2.4-fold) Veg (1.8-fold), Ngfr (1.6-fold) were upregulated, while pro-apoptosis genes such as Bad (-64%), Cstb (-66%) were downregulated. Genes for combating environmental stress (stress response genes) such as Defb3 (2.7-fold), Cygb (2.2-fold), Ahsg (2.18-fold), Alox5 (2-fold) were upregulated. Genes for cell proliferation (cell cycle-related genes) such as Erbb2 (1.84-fold), Mapk12 gene (1.8-fold) was upregulated. Therefore, RR water extracts upregulate many pro-survival genes while downregulating many pro-death genes. It is interpreted that these genes, in combination with other regulated genes, can promote neuronal survival in a stress such as hypoxia.