• Title/Summary/Keyword: PSD-95

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Distinct Regional and Cellular Localization of Hyperpolarization-activated Cyclic Nucleotide-gated Channel 1 in Cerebellar Cortex of Rat

  • Kwon, Young-Joon;Kim, Tae-Sung
    • Journal of Korean Neurosurgical Society
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    • v.42 no.3
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    • pp.205-210
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    • 2007
  • Objective : Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels mediate the hyperpolarization-activated currents (Ih) that participate in regulating neuronal membrane potential and contribute critically to pacemaker activity, promoting synchronization of neuronal networks. However, distinct regional and cellular localization of HCN channels in the brain have not been precisely defined. Aim of this study was to verify the precise cellular location of HCN1 channels in rat cerebellum to better understand the physiological role these channels play in synaptic transmission between CNS neurons. Methods : HCN1 expression in rat brain was analyzed using immunohistochemistry and electron-microscopic observations. Postsynaptic density-95 (PSD-95), otherwise known as locating and clustering protein, was also examined to clarify its role in the subcellular location of HCN1 channels. In addition, to presume the binding of HCN1 channels with PSD-95, putative binding motifs in these channels were investigated using software-searching method. Results : HCN1 channels were locally distributed at the presynaptic terminal of basket cell and exactly corresponded with the location of PSD-95. Moreover, nine putative SH3 domain of PSD-95 binding motifs were discovered in HCN1 channels from motif analysis. Conclusion : Distinct localization of HCN1 channels in rat cerebellum is possible, especially when analyzed in conjunction with the SH3 domain of PSD-95. Considering that HCN1 channels contribute to spontaneous rhythmic action potentials, it is suggested that HCN1 channels located at the presynaptic terminal of neurons may play an important role in synaptic plasticity.

The Effects of Daesiho-tang Extracts on Hypoxic E18 Cortical Neuroblast (대시호탕이 배양신경세포를 이용한 저산소증에 미치는 영향)

  • 김지형;정승현;신길조;문일수;이원철
    • The Journal of Korean Medicine
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    • v.22 no.1
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    • pp.63-77
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    • 2001
  • Objectives : In acute stage of CVA, many patients experience Bugibultong as a symptom. Daesiho-tang is one of the most useful prescriptions for constipated stroke patients. This study investigated the effects of Daesiho-tang extracts on hypoxic E18 cortical neuroblast. Methods : To evaluate the effect of Daesiho-tang extracts on enuronal death caused by hypocia the neuronal viability and protein expressions of NMDA receptor subunits, ${\alpha}CaMK$ II PDE2 PSD95 densin-180, $eEF-l{\alpha}$ and GFAP were investigated. Results : We guessed that Daesiho-tang extracts worked to protect against cell damage through effecting on the protein expression of PSD(post synatpic density), especially increase of ${\alpha}CaMK$ II, $eEF-l{\alpha}$ PDE2, PSD95 and densin-180 Conclusions : According to the above results, it is supposed that Daesiho-tang is clinically applicable to stroke patients in the acute stage.

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Comparative Study of White, Red, and Black Ginseng Extract on Improves the Learning and Memory Impairments by Increases of Synaptic Protein Expression in Scopolamine-induced Dementia Rats

  • Dong Hoon Kwak;Seoul Lee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.38 no.1
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    • pp.38-45
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    • 2024
  • To compare and analyze the improvement effects of white ginseng extract, red ginseng extract, and black ginseng extract on cognitive dysfunction and memory impairment caused by scopolamine in rats. In the cognitive behavioral test, the tendency of the SCOP+B group to overcome the escape time delay induced by scopolamine administration was observed, unlike the SCOP group. The frequency on plat form was significantly increased in the group treated with ginseng extracts compared to the SCOP group. As a result of measuring the duration time on goal quadrant, the time spent in the quadrant was significantly increased in the SCOP+B group compared to the SCOP group. In the hippocampus, the SCOP-treated group significantly decreased the activity of AChE compared to the normal group, but the ginseng extract-treated groups significantly increased it compared to the SCOP group. After sacrificing the rats after the behavioral test, the expression of PSD95 protein in the excised brain was significantly decreased in the SCOP group compared to normal, but it was observed that the SCOP+R and SCOP+B groups were significantly increased compared to the SCOP group. CREB1 protein expression was significantly increased in the SCOP+R group, and the expression of Cdk5 was significantly increased in the SCOP+B group. Ginseng extracts significantly restored the memory damaged by scopolamine suggesting that red ginseng increased the expression of CREB1 and PSD95 proteins, and black ginseng increased the protein expression of Cdk5 and PSD95 to induce memory recovery.

Upregulation by KCI Treatment of Eukaryotic Translation Elongation Factor 1A (eEF1A) mRNA in the Dendrites of Cultured Rat Hippocampal Neurons

  • Moon, Il Soo;Cho, Sun-Jung;Lee, HyunSook;Seog, Dae-Hyun;Jung, Yong Wook;Jin, IngNyol;Walikonis, Randall
    • Molecules and Cells
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    • v.25 no.4
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    • pp.538-544
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    • 2008
  • Activity-dependent local translation in the dendrites of brain neurons plays an important role in the synapse-specific provision of proteins necessary for strengthening synaptic connections. In this study we carried out combined fluorescence in situ hybridization (FISH) and immunocytochemistry (IC) and showed that more than half of the eukaryotic elongation factor 1A (eEF1A) mRNA clusters overlapped with or were immediately adjacent to clusters of PSD-95, a postsynaptic marker, in the dendrites of cultured rat hippocampal neurons. Treatment of the neurons with KCl increased the density of the dendritic eEF1A mRNA clusters more than two-fold. FISH combined with IC revealed that the KCl treatment increased the density of eEF1A mRNA clusters that overlapped with or were immediately adjacent to PSD-95 clusters. These results indicate that KCl treatment increases both the density of eEF1A mRNA clusters and their synaptic association in dendrites of cultured neurons.

Clinical Effect of Acupuncture Combined with Herbal Medicine in Treatment of PSD: A Systematic Review and Meta-Analysis (뇌졸중 후 우울증에 대한 침과 한약의 결합 치료 효과: 체계적 문헌 고찰 및 메타분석 연구)

  • Sakong, Jong-Won;Lim, Su-Yeon;Kim, Sang-Ho;Chung, Dae-kyoo
    • Journal of Oriental Neuropsychiatry
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    • v.31 no.3
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    • pp.169-186
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    • 2020
  • Objectives: The purpose of this study was to provide clinical evidence to support the use of acupuncture combined herbal medicine for post-stroke depression. Methods: Studies were identified by searching Pubmed, EMBASE, Cochrane Library, NDSL, RISS, KMbase, KISS, and CNKI. Randomized controlled trials that verified effects of the acupuncture combined with the herbal medicine for PSD were included in this study. Literature searches of English, Chinese, and Korean databases were performed. Two authors independently extracted the data and assembled the study quality. Results: Of 698 RCTs screened, 17 RCTs were selected. Most of the studies had unclear risk of bias. Among the 17 RCTs, 10 were meta-analyzed. As for the outcome measurement, the effective rate and the HAMD were most commonly used. The meta-analysis of the studies revealed that the PSD cure effective rate in the acupuncture combined with herbal medicine group was higher than that in the Western medicine group (RR: 1.23, 95% CI: 1.14 to 1.33, p<0.00001, I2=0%). Also, the HAMD in the acupuncture combined with herbal medicine group was significantly different compared to the Western medicine group (MD -5.54, 95% CI -9.80 to -1.29, p=0.01, I2=99%). The quality of the selected RCTs was low. Conclusions: Acupuncture combined with herbal medicine is effective for treating post-stroke depression. However, It is worth noting that the included studies were of relatively poor quality. The sample sizes were also small. Based on the findings of this study, further investigations into the diagnosis and treatment of PSD are warranted.

Developmental Expression of Neurofilament 3 (NF-M) in the Cultured Rat Cortical Neurons (배양한 흰쥐 대뇌신경세포에서 신경미세섬유 3(NF-M)의 발생학적 표현)

  • Jung Jae-Seob;Cho Sun-Jung;Jin IngNyol;Jung Seung Hyun;Moon Il Soo
    • Journal of Life Science
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    • v.15 no.4 s.71
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    • pp.600-606
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    • 2005
  • Neurofilament (NF) proteins constitute the major intermediate filament type in adult neurons. They are made up by the copolymerization of the neurofilament light (NF-L, 61 kDa), medium (NF-M, 90kDa), and heavy (NF-H, 115 kDa) proteins. Although neurofilaments play a crucial .ole in neuronal growth, organization, shape, and plasticity, their expression pattern and cellular distribution in the developing neurons remain unknown. In this study, we have produced a rabbit polyclonal antibody specific to NF-M and investigated expression of NF-M in cultured cortical neurons. Immunostaining of 12 and 24 h cultures revealed strong expression of NF-M in axonal growth cone and in the region of a soma toward the axon. Doublestaining of 4 and 14 DIV corical neurons with NF-M and PSD95 antibodies revealed that both axon and dendrites were stained intensely with NF-M antibody, and that NF-M immunostaining along dendrites is often punctate and colocalize with PSD95 puncta, indicating that the puncta represent postsynaptic spines. Presence of NF-M in the postsynaptic spine was also indicated by immunoblot analysis of the postsynaptic density fraction. Taken together, our results show intensive targeting of NF-M into axons in the early axonal development, and into spines in mature neurons, indicating its important functions in axon and spine development.

Oxygen/Glucose Deprivation and Reperfusion Cause Modifications of Postsynaptic Morphology and Activity in the CA3 Area of Organotypic Hippocampal Slice Cultures

  • Jung, Yeon Joo;Suh, Eun Cheng;Lee, Kyung Eun
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.6
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    • pp.423-429
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    • 2012
  • Brain ischemia leads to overstimulation of N-methyl-D-aspartate (NMDA) receptors, referred as excitotoxicity, which mediates neuronal cell death. However, less attention has been paid to changes in synaptic activity and morphology that could have an important impact on cell function and survival following ischemic insult. In this study, we investigated the effects of reperfusion after oxygen/glucose deprivation (OGD) not only upon neuronal cell death, but also on ultrastructural and biochemical characteristics of postsynaptic density (PSD) protein, in the stratum lucidum of the CA3 area in organotypic hippocampal slice cultures. After OGD/reperfusion, neurons were found to be damaged; the organelles such as mitochondria, endoplasmic reticulum, dendrites, and synaptic terminals were swollen; and the PSD became thicker and irregular. Ethanolic phosphotungstic acid staining showed that the density of PSD was significantly decreased, and the thickness and length of the PSD were significantly increased in the OGD/reperfusion group compared to the control. The levels of PSD proteins, including PSD-95, NMDA receptor 1, NMDA receptor 2B, and calcium/calmodulin-dependent protein kinase II, were significantly decreased following OGD/reperfusion. These results suggest that OGD/reperfusion induces significant modifications to PSDs in the CA3 area of organotypic hippocampal slice cultures, both morphologically and biochemically, and this may contribute to neuronal cell death and synaptic dysfunction after OGD/reperfusion.

Effects of Water-Extracts of Bambusae concretio silicae(BCS, 天竺黃) on the Expression of Neurotransmitter Receptors (천죽황(Bambusae concretio silicae, 天竺黃) 물추출물이 신경전달물질 수용체의 표현에 미치는 영향)

  • Yoon, Jae-Hong;Kim, Kyung-Min;Kim, Kyung-Hun;Shin, Gil-Cho;Jeong, Seung-Hyun
    • Journal of Oriental Neuropsychiatry
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    • v.22 no.2
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    • pp.163-176
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    • 2011
  • Objectives : BCS(Bambusae concretio silicae) is used as a traditional medicine in Korea for the incipient stroke. Recent reports indicated that BCS has a neuroprotective effect by anti-convulsion effect. However, it's mechanism is not well studied. The purpose of this study was to investigate into the molecular mechanism of BCS for neuroprotection in normoxia of cultured rat hippocampal neurons. Methods : BCS (1.0, 2.5, 5.0, and $10.0\;{\mu}g/m{\ell}$) was added to culture media (Neurobasal supplemented with B27) on DIV 0, given a normoxia, and the cell viability was measured by typical phase-contrast images of the cultures with 1.0, 2.5, 5.0, and $10.0\;{\mu}g/m{\ell}$ on DIV 21. Effects of BCS on the expression of various synaptic proteins ($GABA_B$ R1, $GABA_B$ R2, GlyR, PSD95) were observed by immunocytochemistry showing on DIV 3, 7 and 21. Results : Typical phase-contrast images of the cultures indicated that BCS has a protective effect of rat hippocampal cells in normoxia. The BCS upregulated $GABA_B$ R1 after normoxia on DIV 7, $GABA_A$ ${\beta}2/3$ on DIV 21 and $GABA_B$ R2 on DIV 21. And the BCS downregulated PSD95 after normoxia on DIV 7. Conclusions : The present study showed evidence for the efficacy of BCS in Typical phase-contrast images, upregulation of inhibitory neurotransmitter receptors($GABA_B$ R1) and downregulation of PSD95 which eventually protected neuronal cell death in normoxia.