• Title/Summary/Keyword: hippocampal neurons

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The Neuroprotective Effects of InSamYangYoung-tang(Renshenyangrongtang) on Aβ-induced Damages in Mice (인삼양영탕(人蔘養榮湯)이 Aβ를 처리한 PC12 세포와 생쥐의 손상 뇌신경조직에 미치는 영향)

  • Jang, Young-Joo;Jung, In-Chul;Lee, Sang-Ryong
    • Journal of Oriental Neuropsychiatry
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    • v.21 no.1
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    • pp.109-124
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    • 2010
  • Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

Neuroprotective and Anti-Oxidative Effect of Puerariae Radix on Hippocampal Neurons and BV-2 Microglia Cells (갈근(葛根)의 뇌해마(腦海馬) 신경세포 손상보호와 항산화(抗酸化) 효능에 대한 연구)

  • Kim, Sang-Hyun;Kim, Youn-Sub
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.2
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    • pp.416-425
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    • 2005
  • This study demonstrated neuroprotective and anti-oxidative effects of Puerariae Radix for cerebral ischemia. Neuroprotective effects were studied by using oxygen/glucous deprivation of the organotypic hippocampal slice cultures to complement limitations of in vivo and in vitro models for cerebral ischemia study. Anti-oxidative effects were studied on BV-2 microglia cells damaged by $H_2O_2$ and nitric oxide. The results obtained are as follows; The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in CA1 region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in DG region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of TUNEL-positive cells in both CA1 region and DG region of ischemic damaged hippocampus cultures. The group treated with $50\;{\mu}g/m{\ell}$ of Puerariae Radix demonstrated significant decrease of TUNEL-positive cells in CA1 region. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of LDH concentrations in culture media of ischemic damaged hippocampus cultures. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant increases of cell viabilities of BV-2 microglia cells damaged by $H_2O_2$. The group treated with $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant increase of cell viability of BV-2 microglia cells damaged by nitric oxide. These results suggested that Puerariae Radix of cerebral ischemic revealed neuroprotective effects through the control effect of apoptosis and oxidative damages.

Protective effect of Shenqi-wan and its fractions on N-methyl-D-aspartate-induced excitotoxicity in rat hippocampus

  • Lee, Joung-Hun;Kim, Youn-Sub;Kim, Young-Sick;Kim, Sung-Eun;Sung, Yun-Hee;Kim, Bo-Kyun;Lee, Jin-Woo;Ham, Dae-Hyun;Lee, Hye-Jung;Kim, Chang-Ju
    • Advances in Traditional Medicine
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    • v.7 no.5
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    • pp.534-539
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    • 2008
  • Shenqi-wan, Oriental herbal medicine formulation, has traditionally been used for the treatment of delayed mental and physical development in children, complications of diabetes, and glomerulonephritis. In the present study, we investigated the protective effect of the aqueous extract of Shenqi-wan and its fractions against N-methyl-D-aspartate (NMDA)-induced exitotoxicity in rat hippocampal CA1 neurons. Fractions were elucidated at 0 - 10 min, 11 - 20 min, and 21 - 30 min by using gravity column chromatography method. In the present results, treatment with NMDA on cultured hippocampal slices induced neuronal death in the hippocampal CA1 region. Pretreatment with the Shenqi-wan did not exerted protective effect, however its fractions suppressed NMDA-induced neuronal damage. The fraction elucidated at 11 - 20 min showed the most potent protective effect. These results revealed that effective substances of the Shenqi-wan against NMDA-induced excitotoxicity may exist mainly in the fraction elucidated at 11 - 20 min.

Effect of Glial-neuronal Cell Co-culture on GFAP Expression of Astrocytes (신경세포가 별아교세포의 아교섬유성 산단백질 표현에 미치는 영향)

  • Bae Hyung-Mi;Park Jung-Sun;Yeon Dong-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.3
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    • pp.285-296
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    • 1997
  • Injury to brain transforms resting astrocytes to their reactive form, the hallmark of which is an increase in glial fibrillary acidic protein (GFAP), the major intermediate filament protein of their cell type. The overall glial response after brain injury is referred to as reactive gliosis. Glial-neuronal interaction is important for neuronal migration, neurite outgrowth and axonal guidance during ontogenic development. Although much attention has been given to glial regulation of neuronal development and regeneration, evidences also suggest a neuronal influence on glial cell differentiation, maturation and function. The aim of the present study was to analyze the effects of glial-hippocampal neuronal co-culture on GFAP expression in the co-cultured astrocytes. The following antibodies were used for double immunostaining chemistry; mouse monoclonal antibodies for confirm neuronal cells, rabbit anti GFAP antibodies for confirm astrocytes. Primary cultured astrocytes showed the typical flat polygonal morphology in culture and expressed strong GFAP and vimentin. Co-cultured hippocampal neurons on astrocytes had phase bright cell body and well branched neurites. About half of co-cultured astrocytes expressed negative or weak GFAP and vimentin. After 2 hour glutamate (0.5 mM) exposure of glial-neuronal co-culture, neuronal cells lost their neurites and most of astrocytes expressed strong CFAE and vimentin. In Western blot analysis, total GFAP and vimentin contents in co-cultured astrocytes were lower than those of primary cultured astrocytes. After glutamate exposure of glial-neuronal co-culture, GFAP and vimentin contents in astrocytes were increased to the level of primary cultured astrocytes. These results suggest that neuronal cell decrease GFAP expression in co-cultured astrocytes and hippocampal neuronal-glial co-culture can be used as a reactive gliosis model in vitro for studying GFAP expression of astrocytes.

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Effects of Glutamate Receptor Antagonists and Protein Synthesis Inhibitor on Delayed Neuronal Death Induced by Transient Global Ischemia in Rat Brain

  • Ko, Jun-Seog;Bae, Choon-Sang;Kim, Jong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.3
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    • pp.279-286
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    • 1998
  • It has been well documented that transient forebrain global ischemia causes selective neuronal degeneration in hippocampal CA1 pyramidal neurons with a delay of a few days. The mechanism of this delayed hippocampal CA1 pyramidal neuronal death (DND) is still controversial. To delineate the mechanisms of the DND, the effects of treatment with MK-801, an NMDA receptor antagonist, kynurenic acid, a NMDA/non-NMDA receptor antagonist, and/or cycloheximide, a protein synthesis inhibitor, on the DND were investigated in male Wistar rats. To examine the participation of apoptotic neuronal death in the DND, TUNEL staining was performed in ischemic brain section. Global ischemia was induced by 4-vessel occlusion for 20 min. All animals in this study showed the DND 3 and 7 days after the ischemic insult. The DND that occured 3 days and 7 days after the ischemia were not affected by pretreatment with MK-801 (1 mg/kg), but markedly attenuated by the pretreatment with kynurenic acid (500 mg/kg). Treatment with cycloheximide (1 mg/kg) also markedly inhibited the DND. The magnitudes of attenuation by the two drugs were similar. The magnitude of attenuation by co-treatments with kynurenic acid and cycloheximide was not greater than that with any single treatment. TUNEL staining was negative in the sections obtained 1 or 2 days after the ischemic insults, but it was positive at hippocampal CA1 pyramidal cells in sections collected 3 days after the ischemia. These results suggested that the DND should be mediated by the activation of non-NMDA receptor, not by the activation of NMDA receptor and that the activation of AMPA receptor should induce the apoptotic process in the DND.

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Antidepressant-like effect of ginsenoside Rb1 on potentiating synaptic plasticity via the miR-134-mediated BDNF signaling pathway in a mouse model of chronic stress-induced depression

  • Wang, Guoli;An, Tianyue;Lei, Cong;Zhu, Xiaofeng;Yang, Li;Zhang, Lianxue;Zhang, Ronghua
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.376-386
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    • 2022
  • Background: Brain-derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) plays a critical role in the pathogenesis of depression by modulating synaptic structural remodeling and functional transmission. Previously, we have demonstrated that the ginsenoside Rb1 (Rb1) presents a novel antidepressant-like effect via BDNF-TrkB signaling in the hippocampus of chronic unpredictable mild stress (CUMS)-exposed mice. However, the underlying mechanism through which Rb1 counteracts stress-induced aberrant hippocampal synaptic plasticity via BDNF-TrkB signaling remains elusive. Methods: We focused on hippocampal microRNAs (miRNAs) that could directly bind to BDNF and are regulated by Rb1 to explore the possible synaptic plasticity-dependent mechanism of Rb1, which affords protection against CUMS-induced depression-like effects. Results: Herein, we observed that brain-specific miRNA-134 (miR-134) could directly bind to BDNF 30 UTR and was markedly downregulated by Rb1 in the hippocampus of CUMS-exposed mice. Furthermore, the hippocampus-targeted miR-134 overexpression substantially blocked the antidepressant-like effects of Rb1 during behavioral tests, attenuating the effects on neuronal nuclei-immunoreactive neurons, the density of dendritic spines, synaptic ultrastructure, long-term potentiation, and expression of synapse-associated proteins and BDNF-TrkB signaling proteins in the hippocampus of CUMS-exposed mice. Conclusion: These data provide strong evidence that Rb1 rescued CUMS-induced depression-like effects by modulating hippocampal synaptic plasticity via the miR-134-mediated BDNF signaling pathway.

Effect of growth hormone on neuronal death in hippocampal slice cultures of neonatal rats exposed to oxygen-glucose deprivation (신생 흰쥐 해마 절편 배양에서 산소-포도당 박탈에 의한 신경 세포 사망에 대한 성장호르몬의 효과)

  • Hong, Kyung Sik;Gang, Jihui;Kim, Myeung Ju;Yu, Jeesuk;Chang, Young Pyo
    • Clinical and Experimental Pediatrics
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    • v.52 no.5
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    • pp.588-593
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    • 2009
  • Purpose : To investigate whether growth hormone (GH) has a protective effect on neurons in hippocampal slice cultures of neonatal rats exposed to oxygen-glucose deprivation (OGD). Methods : Cultured hippocampal slices of 7-day-old rats were exposed to OGD for 60 min. Then, the slices were immediately treated with three doses of GH (5, 50, or $500{\mu}M$) in media. The relative fluorescent densities of propidium iodide (PI) uptake in the slices and relative lactate dehydrogenase (LDH) activities in the media were determined and compared between each GH- treated group of slices and untreated slices (control) at 12 and 24 h after OGD. Immunofluorescent staining for caspase-3 and TUNEL staining were performed to observe the effect of GH on apoptotic neuronal death. Results : The relative fluorescent densities of PI uptake in CA1 and dentate gyrus (DG) of the hippocampal slices in each GH-treated group were not significantly different from those in the untreated slices at 12 and 24 h after OGD (P>0.05). Treatment with GH could reduce the relative LDH activities in the media of the GH-treated groups only at 12 h after OGD (P<0.05). Expression of caspase-3 and TUNEL positivity in CA1 and DG of the slices treated with 50-iM GH were not different from those of the untreated slices at 12 and 24 h after OGD. Conclusion : Treatment of hippocampal slice cultures with GH after OGD does not show a definitive protective effect on neuronal death but can reduce the LDH efflux of the slices in media at 12 h after OGD.

Water Extract of Rhei Rhizoma Prevent Production of Reactive Oxygen Species and Loss of Mitochondrial Membrane Potential in a Hypoxia Model of Cultured Neurons (배양 신경세포의 저산소증모델에서 대황 물추출액의 항산화 및 사립체막전위 소실 억제 효능)

  • Lee, Hyun-Sook;Moon, Il-Soo
    • Journal of Life Science
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    • v.18 no.12
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    • pp.1631-1636
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    • 2008
  • Rhei Rhizoma (RR; 大黃) consists of the underground parts (rhizome and root) of Rheum officinale Baill. and Rheum palmatum L. (Polygonaceae), and is widely used in Southeast Asian folk medicine to alleviate liver and kidney damages. In this study, we investigated into the efficacy and mechanism of RR water extract in supporting neuronal survival in a hypoxia model of cultured rat hippocampal neurons. RR exhibited no cytotoxicity up to 10 ${\mu}g$/ml and exhibited neurosupportive effects at 2.5 ${\mu}g$/ml in normoxia. When RR was added to the culture media on 10 days in vitro (DIV10) and given a hypoxic shock (2% $O_2$/5% $CO_2$, 3 hr, $37^{\circ}C$) on DIV13, RR exhibited neuroprotective effects on 5 days post-shock. $H_2DCF$ stainings indicated that RR effectively prevents ROS production in both normoxia and hypoxia. JC-1 stainings showed that RR prevents dissipation of MMP in hypoxia. These results indicate that RR protects neurons by suppressing ROS production and MMP loss.

The Dose-dependent Effects of Guibi-Tang on Focal Brain Ischemic Injury in Rats (귀비탕(歸脾湯)의 농도별(濃度別) 구강투여(口腔投與)가 백서(白鼠)의 허혈성(虛血性) 뇌손상(腦損傷)에 미치는 영향(影響))

  • Gug, Yun-Jai;Park, Jang-Ho;Kim, Jin-Hyung;Kim, Hyang-Yi;Kang, Hyung-Won;Lyu, Yeoung-Su
    • Journal of Oriental Neuropsychiatry
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    • v.22 no.4
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    • pp.201-218
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    • 2011
  • Objectives : The aim of this study was to investigate the effects of Guibi-Tang(GBT) on focal brain ischemic injury induced by intraluminal filament insertion in rats. Methods : The ischemia was induced by intraluminal filament insertion into middle cerebral artery. Sprague-Dawley rats were divided into five groups, normal group(n=8); control group was ischemia induced and no treatment(n=8); GBT 1X group was ischemia induced and administrated 42.2 mg/ml/kg of Guibi-Tang orally(n=8); GBT 3X group was ischemia induced and administrated 126.6 mg/ml/kg of Guibi-Tang orally(n=8); GBT 6X group was ischemia induced and administrated 253.2 mg/ml/kg of Guibi-Tang orally(n=8) for 21 days. mGluR5, Bax, Bcl-2 and cytochrome C were investigated to observe the effects of Guibi-Tang on apoptosis. The effects of Guibi-Tang on neuroprotective/apoptotic agents in cresyl violet, choline acetyltranferase(ChAT) with ischemic injury were investigated. Results : The intensity of mGluR5 mRNA in the hippocampal CA1 was increased in normal and GBT(Guibi-Tang) 1X groups compared with the control group. The intensity of Bax mRNA in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. However it was increased unexpectedly in GBT 3X group. The intensity of Bcl-2 mRNA in the hippocampal CA1 was increased in normal and GBT 1X groups compared with the control group. The intensity of Bax/Bcl-2 ratio in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. The intensity of cytochrome C protein in the hippocampal CA1 was decreased in normal, GBT 1X and GBT 6X groups compared with the control group. The density of neurons stained by cresyl violet and ChAT was increased in normal and GBT 1X groups compared with the control group. Conclusions : These results suggest that Guibi-Tang may have protective effect on vascular dementia.

Pre-ischemic Treatment with Ampicillin Reduces Neuronal Damage in the Mouse Hippocampus and Neostriatum after Transient Forebrain Ischemia

  • Lee, Kyung-Eon;Kim, Seul-Ki;Cho, Kyung-Ok;Kim, Seong-Yun
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.6
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    • pp.287-291
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    • 2008
  • Ampicillin, a $\beta$-lactam antibiotic, has been reported to induce astrocytic glutamate transporter-l which plays a crucial role in protecting neurons against glutamate excitotoxicity. We investigated the effect of ampicillin on neuronal damage in the mouse hippocampus and neostriatum following transient global forebrain ischemia. Male C57BL/6 mice were anesthetized with halothane and subjected to bilateral occlusion of the common carotid artery for 40 min. Ampicillin was administered post-ischemically (for 3 days) and/or pre-ischemically (for $3{\sim}5$ days until one day before the onset of ischemia). Pre- and post-ischemic treatment with ampicillin (50 mg/kg/day or 200 mg/kg/day) prevented ischemic neuronal death in the medial CAI area of the hippocampus as well as the neostriatum in a dose-dependent manner. In addition, ischemic neuronal damage was reduced by pre-ischemic treatment with ampicillin (200 mg/kg/day). In summary, our results suggest that ampicillin plays a functional role as a chemical preconditioning agent that protects hippocampal neurons from ischemic insult.