• 생명과학회지
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• 제26권12호
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• pp.1458-1465
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• 2016

본 연구는 oxidative stress에 의한 세포죽음 분석의 이상적인 모델로 사용되는 HT22세포를 이용하여 천문동 에탄올추출물의 glutamate에 의한 oxidative toxicity에 대한 신경보호 효과를 살펴보았다. 이를 위해 cell viability, lactate dehydrogenase (LDH), 그리고 세포죽음형태, reactive oxygen species (ROS), mitochondria membrane potential (MMP) 등에 대한 flow cytometry 및 Western blot분석을 이용하였다. 천문동 추출물의 처리는 cell viability 및 LDH분석에서 glutamate에 의한 cell toxicity를 저하시키며, 특히 apoptotic cell death를 현저히 감소시켰다. ROS 및 MMP분석 결과, 천문동 추출물은 ROS의 형성을 저하시키며 glutamate에 의해 저하된 MMP를 현저히 회복시켜 주었다. 이와 관련된 단백질 발현을 보면, 천문동 추출물은 PARP 및 HO-1의 발현을 억제하였다. 이상의 결과는 천문동 추출물이 HT22해마세포에서 ROS형성저해 및 MMP회복에 의해 세포죽음을 완화시켜 보호작용을 하는 것으로 사료되며 oxidative toxicity관련 질환에 적용 가능할 것으로 보여 진다.

• Journal of Ginseng Research
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• 제44권3호
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• pp.490-495
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• 2020

Background: Ginsenoside Rk1, a saponin component isolated from heat-processed Panax ginseng Meyer, has been implicated in the regulation of antitumor and anti-inflammatory activities. Although our previous studies have demonstrated that ginsenoside Rg3 significantly attenuated the activation of NMDA receptors (NMDARs) in hippocampal neurons, the effects of ginsenosides Rg5 and Rk1, which are derived from heat-mediated dehydration of ginsenoside Rg3, on neuronal NMDARs have not yet been elucidated. Methods: We examined the regulation of NMDARs by ginsenosides Rg5 and Rk1 in cultured rat hippocampal neurons using fura-2-based calcium imaging and whole-cell patch-clamp recordings. Results: The results from our investigation showed that ginsenosides Rg3 and Rg5 inhibited NMDARs with similar potencies. However, ginsenoside Rk1 inhibited NMDARs most effectively among the five compounds (Rg3, Rg5, Rk1, Rg5/Rk1 mixture, and protopanaxadiol) tested in cultured hippocampal neurons. Its inhibition is independent of the NMDA- and glycine-binding sites, and its action seems to involve in an interaction with the polyamine-binding site of the NMDAR channel complex. Conclusion: Taken together, our results suggest that ginsenoside Rk1 might be a novel component contributable to the development of ginseng-based therapeutic treatments for neurodegenerative diseases.

• Journal of Medicine and Life Science
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• 제15권2호
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• pp.67-71
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• 2018

Neuronal excitotoxicity induces mitochondrial dysfunction and the release of proapoptotic proteins. Excitotoxicity, the process by which the overactivation of excitatory neurotransmitter receptors leads to neuronal cell death. Neuronal death by excitotoxicity was related to neuronal degenerative disorders and hypoxia, results from excessive exposure to excitatory neurotransmitters, such as glutamate. Glutamate acts at NMDA receptors in cultured neurons to increase the intracellular free calcium concentration. Therefore endogenous glutamate may be a key factor to regulate neuronal cell death via activating $Ca^{2+}$ signaling. For this issue, we tested some conditions to alter intracellular $Ca^{2+}$ level in dissociated hippocampal neurons of rats. Cultured hippocampal neuron were treated by KCl (20 mM), $CaCl_2$ (3.8 mM) and glutamate ($5{\mu}M$) for 24 hrs. Interestingly, The Optical Density of hippocampal neurons was increased by high KCl application in MTT assay data. This enhanced response by high KCl was dependent on synaptic $Ca^{2+}$ influx but not on intracellular $Ca^{2+}$ level. However, the number of neurons seemed to be not changed in Hoechst 33342 staining data. These results suggest that enhancement of synaptic activity plays a key role to increase mitochondrial signaling in hippocampal neurons.

• 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.

• Toxicological Research
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• 제27권2호
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• pp.103-110
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• 2011

Lipotoxicity involves pathological alterations to cells and tissues in response to elevated fat levels in blood. Furthermore, this process can disturb both cellular homeostasis and viability. In the current study, the authors show that neural progenitor cells (NPCs) are vulnerable to high levels of palmitic acid (PA) a saturated fatty acid. PA was found to cause cell death associated with elevated reactive oxygen species (ROS) levels, and to reduce NPCs proliferation. To evaluate the lipotoxicity of PA in adult NPCs in the hippocampus, male C57BL/6 mice were divided into two groups and maintained on either a normal diet (ND) or PA-rich high fat diet (HFD) for 2 weeks. Interestingly, short-term PA-rich HFD feeding reduced the survival of newly generated cells in the hippocampal dentate gyrus and hippocampal brain-derived neurotrophic factor levels. These findings suggest PA has a potent lipotoxicity in NPCs and that a PA-rich HFD disrupts hippocampal neurogenesis.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2006년도 제47회 학술심포지움 및 추계국제학술대회
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• pp.73.1-73.1
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• 2006

• 운동영양학회지
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• 제13권2호
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• pp.147-153
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• 2009

Effect of whole body vibration exercise on intracerebral hemorrhage in rats. Intracerebral hemorrhage is one of the most devastating types of stroke. This disease is known to cause severe neurological damage and also has a very high mortality rate. In the present study, the effects of whole body vibration exercise on memory capability and apoptotic neuronal cell death in the hippocampal CA1 region following intracerebral hemorrhage in rats were investigated. Intracerebral hemorrhage was induced by injection of collagenase into the hippocampal CA1 region using a stereotaxic instrument. The rats were divided into 5 groups: the sham-operation group, the hemorrhage-induction group, the hemorrhage-induction and 8 Hz vibration exercise group, the hemorrhage-induction and 16 Hz vibration exercise group, and the hemorrhage-induction and 24 Hz vibration exercise group. The animals in the whole body vibration exercise groups received whole body vibration at 8 Hz, 16 Hz, and 24 Hz, respectively for 30 min once a day during 14 consecutive days. In the present results, the apoptotic neuronal cell death in the hippocampal CA1 region was significantly increased following induction of intracerebral hemorrhage, resulting in memory impairment. Whole body vibration exercise suppressed hemorrhage-induced apoptosis in the hippocampal CA1 region. This suppressive effect of whole body vibration exercise also alleviated hemorrhage-induced memory impairment. Here in this study, we have shown that whole body vibration exercise inhibited intracerebral hemorrhage-induced apoptotic neuronal cell death and thus facilitated recovery of brain function following intracerebral hemorrhage.

• 대한감각통합치료학회지
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• 제2권1호
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• pp.21-32
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• 2004

Objective : Effect of treadmill exercise on hippocampal neural cell proliferation under normal conditions and alcohol intoxication conditions has been recently studied; however, this effect under sensory stimulation application has not clarified yet. In the present study, the effect of compression stimulation application on hippocampal neural cell proliferation in the dentate gyrus in normal and alcohol intoxicated rats was investigated. Methods : Experimental design: comparative investigation on number of 5-Bromo-2'-deoxyuridine(BrdU)B-positive cells in dentate gyrus 5 days after commencement. Setting: animal laboratory. Participants: male Sprague-Dawley rats of 3weeks old in age weighing $80{\pm}10gm$. Intervention: animals were randomly assigned into 4 groups; control-rest group(n=8), control-compression group(n=8), alcohol intoxication-rest group(n=8) and alcohol intoxication-compression group(n=8). Animals of the alcohol intoxicated groups were injected intraperitoneally with alcohol(2g/kg) twice per day for 3 days. All animals were injected BrdU(50mg/kg) intraperitoneally, and rats compression stimulation application groups were compressed using sphygmomanometer cuff times per day, for 5 days following alcohol administration. Measures: mean number of BrdU-positive cells in dentate gyrus was observed via immunohistochemistry. Results : Compression stimulation application significantly increased the number of BrdU-positive cells in the dentate gyrus. Also, treatment with alcohol for 3 days inhibited cell proliferation, and compression stimulation application alleviated alcohol-induced inhibition of new cell formation. Conclusion : These results suggest the possibility that compression stimulation application may help in improvement following alcohol-induced brain damaged.

• Animal cells and systems
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• 제16권3호
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• pp.190-197
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• 2012

Depression is one of the most prevalent diseases of alcohol abuse. Brain-derived neurotrophic factor (BDNF) plays a critical role in cell survival in the hippocampus. Phosphorylation of extracellular signal-regulated kinase 1/2 (p-ERK1/2) is induced by BDNF, and it regulates cell proliferation and differentiation in the brain. We investigated the effects of alcohol intake on depression-like behavior, cell proliferation, expressions of BDNF and its downstream molecules in the hippocampus using Mongolian gerbils. The gerbils were divided into four groups: control group, 0.5 g/kg alcohol-treated group, 1 g/kg alcohol-treated group, 2 g/kg alcohol-treated group. Each dose of alcohol was orally administered for 3 weeks. The present results demonstrated that alcohol intake induced depression-like behavior. Both 5-hydroxytryptamine synthesis and its synthesizing enzyme tryptophan hydroxylase expression in the dorsal raphe and cell proliferation in the hippocampal dentate gyrus were decreased by alcohol intake. Alcohol intake suppressed BDNF expression, and resulted in the decrease of its downstream molecules, pERK1/2 and Bcl-2, in the hippocampus. We showed that alcohol intake may lead to a depressed-like state with reduced hippocampal cell proliferation through inhibition of the BDNF-ERK signaling pathway.

• Journal of Ginseng Research
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• 제33권4호
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• pp.294-304
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• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of various symptoms in South Korea. The neuroprotective effects of ginsenoside $Rg_3$ (G-$Rg_3$) on cholesterol-oxide-(CO)-induced neurotoxicity were investigated through the analyses of rat brains. The recently accumulated reports show that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, the neuroprotective effects of G-$Rg_3$ on CO-induced hippocampal excitotoxicity were examined in vivo. The in-vitro studies using rat cultured hippocampal neurons revealed that G-$Rg_3$ treatment significantly inhibited CO-induced hippocampal cell death. G-$Rg_3$ treatment not only significantly reduced CO-induced DNA damage but also attenuated CO-induced apoptosis. The in-vivo studies that were conducted revealed that the intracerebroventricular (i.c.v.) pre-administration of G-$Rg_3$ significantly reduced i.c.v. CO-induced hippocampal damage in rats. To examine the mechanisms underlying the in-vitro and in-vivo neuroprotective effects of G-$Rg_3$ against CO-induced hippocampal excitotoxicity, the effect of G-$Rg_3$ on the CO-induced elevations of the apoptotic cells in cultured hippocampal cells was examined, and it was found that G-$Rg_3$ treatment inhibited CO-induced apoptosis. The histopathological evaluation demonstrated that G-$Rg_3$ significantly diminished the apoptosis in the hippocampus and also spared the hippocampal CA1, CA3, and dentate gyrus neurons. G-$Rg_3$ also significantly improved the CO-caused behavioral impairment. G-$Rg_3$ itself had no effect, however, on the CO-induced inhibition of succinate dehydrogenase activity (data not shown). These results collectively indicate the G-$Rg_3$-induced neuroprotection against CO in rat hippocampus. With regard to the wide use of G-$Rg_3$, this agent is potentially beneficial in treating CO-induced brain injury.