• Title/Summary/Keyword: neuronal

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The underlying mechanism of calcium toxicity-induced autophagic cell death and lysosomal degradation in early stage of cerebral ischemia

  • Jirakhamon Sengking;Pasuk Mahakkanukrauh
    • Anatomy and Cell Biology
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    • v.57 no.2
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    • pp.155-162
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    • 2024
  • Cerebral ischemia is the important cause of worldwide disability and mortality, that is one of the obstruction of blood vessels supplying to the brain. In early stage, glutamate excitotoxicity and high level of intracellular calcium (Ca2+) are the major processes which can promote many downstream signaling involving in neuronal death and brain tissue damaging. Moreover, autophagy, the reusing of damaged cell organelles, is affected in early ischemia. Under ischemic conditions, autophagy plays an important role to maintain energy of the brain and its function. In the other hand, over intracellular Ca2+ accumulation triggers excessive autophagic process and lysosomal degradation leading to autophagic process impairment which finally induce neuronal death. This article reviews the association between intracellular Ca2+ and autophagic process in acute stage of ischemic stroke.

Neuronal injury in AIDS dementia: Potential treatment with NMDA open-channel blockers and nitric oxide-related species

  • Lipton, Stuart A.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.19-29
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    • 1996
  • The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

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Isolation of human mesenchymal stem cells from the skin and their neurogenic differentiation in vitro

  • Byun, Jun-Ho;Kang, Eun-Ju;Park, Seong-Cheol;Kang, Dong-Ho;Choi, Mun-Jeong;Rho, Gyu-Jin;Park, Bong-Wook
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.38 no.6
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    • pp.343-353
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    • 2012
  • Objectives: This aim of this study was to effectively isolate mesenchymal stem cells (hSMSCs) from human submandibular skin tissues (termed hSMSCs) and evaluate their characteristics. These hSMSCs were then chemically induced to the neuronal lineage and analyzed for their neurogenic characteristics in vitro. Materials and Methods: Submandibular skin tissues were harvested from four adult patients and cultured in stem cell media. Isolated hSMSCs were evaluated for their multipotency and other stem cell characteristics. These cells were differentiated into neuronal cells with a chemical induction protocol. During the neuronal induction of hSMSCs, morphological changes and the expression of neuron-specific proteins (by fluorescence-activated cell sorting [FACS]) were evaluated. Results: The hSMSCs showed plate-adherence, fibroblast-like growth, expression of the stem-cell transcription factors Oct 4 and Nanog, and positive staining for mesenchymal stem cell (MSC) marker proteins (CD29, CD44, CD90, CD105, and vimentin) and a neural precursor marker (nestin). Moreover, the hSMSCs in this study were successfully differentiated into multiple mesenchymal lineages, including osteocytes, adipocytes, and chondrocytes. Neuron-like cell morphology and various neural markers were highly visible six hours after the neuronal induction of hSMSCs, but their neuron-like characteristics disappeared over time (24-48 hrs). Interestingly, when the chemical induction medium was changed to Dulbecco's Modified Eagle Medium (DMEM) supplemented with fetal bovine serum (FBS), the differentiated cells returned to their hSMSC morphology, and their cell number increased. These results indicate that chemically induced neuron-like cells should not be considered true nerve cells. Conclusion: Isolated hSMSCs have MSC characteristics and express a neural precursor marker, suggesting that human skin is a source of stem cells. However, the in vitro chemical neuronal induction of hSMSC does not produce long-lasting nerve cells and more studies are required before their use in nerve-tissue transplants.

Antioxidative Activity of Extracts from Cichorium endivia L. (치콘 추출물의 항산화 활성)

  • Kang, Hyun Woo
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.11
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    • pp.1487-1492
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    • 2012
  • Antioxidant activity and neuroprotective effects of extracts from Cichorium endivia L. (CEL) on hydrogen peroxide-induced oxidative damage in neuronal cells were investigated. The total polyphenol and flavonoid contents of the water and ethanolic extracts from CEL were $36.2{\pm}0.99$, $37.2{\pm}3.76$ mg gallic acid equivalent/g extract, and $46.9{\pm}5.22$, $53.86{\pm}5.09$ mg catechin equivalent/g extract, respectively. In addition, antioxidant activities of the extracts were also determined by ferric reducing antioxidant power (FRAP), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and reducing power. In an MTT assay on the neuronal cells, the extracts showed a protective effect by increasing cell viability on hydrogen peroxide-induced oxidative damage in neuronal cells. Antioxidative enzyme (superoxide dismutase: SOD, catalase: CAT) levels in cultured neuronal cells were increased in the presence of extracts from CEL. It was found that CEL extracts inhibited hydrogen peroxide-induced Bcl-2 and Bax expression in neuronal cells. These results indicate that the CEL extracts possess an antioxidant activity.

The Effect of Topiramate on Hippocampal Neuronal Death and Expression of Glutamate Receptor in Kainate-induced Status Epilepticus Model (Kainate 유발 간질중첩증 모델에서 topiramate가 해마 신경세포사와 glutamate 수용체 발현에 미치는 영향)

  • Park Min-Jeong;Ha Se-Un;Bae Hae-Rahn;Kim Sang-Ho
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.505-512
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    • 2005
  • Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.

SYNCHRONIZATION OF UNIDIRECTIONAL RING STRUCTURED IDENTICAL FITZHUGH-NAGUMO NETWORK UNDER IONIC AND EXTERNAL ELECTRICAL STIMULATIONS

  • Ibrahim, Malik Muhammad;Jung, Il Hyo
    • East Asian mathematical journal
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    • v.36 no.5
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    • pp.547-554
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    • 2020
  • Synchronization of unidirectional identical FitzHugh-Nagumo systems coupled in a ring structure under ionic and external electrical stimulations is investigated. In this network, each neuron is only connected and transmit signals to its next neuron via synaptic strength called gapjunctions. Adaptive control theory and Lyapunov stability theory are used to propose a unique control scheme with necessary and sufficient conditions which guarantee the synchronization of the neuronal network. Finally, the effectiveness of the proposed scheme is shown through numerical simulations.

Therapeutic Intervention of Aggregate Formation in Huntington's Disease: A Potential Role of Tissue Transglutaminase (tTG)

  • Chun, Wan-Joo
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.65-66
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    • 2003
  • The cause of Huntington's disease (HD) is a pathological expansion of the polyglutamine domain within the N-terminal region of huntingtin. Neuronal aggregates composed of mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. Because tissue transglutaminase (tTG) cross-links proteins into aggregates and polypeptide-bound glutamines are primary determining factors for tTG-catalyzed reactions, it has been hypothesized that tTG may contribute to the formation of aggregates. (omitted)

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Zinc-induced Neurotoxicity and Its Role in Brain Diseases

  • Koh, Jae-Young
    • Proceedings of the Korean Biophysical Society Conference
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    • 1998.06a
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    • pp.14-14
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    • 1998
  • Mammalian brian contains substantial amounts of chelatable zinc in presynaptic vesicles of certain glutamatergic terminals. The synaptic zinc is released with intense neuronal activity, suggesting its role in synaptic transmission. However, in pathological conditions, zinc may get released too excessively, which may contribute to neuronal death as shown in cortical cultures.(omitted)

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Induction of Demyelination by Infection of Semliki Forest Virus

  • Kim, Hyun Joo;Choi, Chang-Shik;Hong, Seong-Karp
    • Rapid Communication in Photoscience
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    • v.5 no.1
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    • pp.11-12
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    • 2016
  • Schwann cells and neuronal cells from dorsal root ganglion (DRG) in embryos of rat were cultured in vitro respectively. The purified neuronal cells with anti-mitotic agents and purified Schwann cells were co-cultured and then accomplished myelination processing. Infection of Semliki forest virus into this myelinated co-culture system was performed and then accomplished demyelination. We identified myelination and demyelination processing using antibody of neuropeptide Y.

Purinergic-mediated Calcium Homeostasis and Dopamine R~lease in PC 12 Cells: Effect of Ethanol

  • Kim, Won-Ki
    • Proceedings of the Korean Biophysical Society Conference
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    • 1997.07a
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    • pp.16-16
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    • 1997
  • Extracelluar ATP evokes many biological processes, including neuronal excitation and neurotransmitter secretion, through activation of purinergic P2 receptors. Although excitatory and inhibitory receptor-operated channels (ROC) and voltage-dependent calcium channels (VDCC) have been reported to be altered by acute and chronic exposure to ethanol, little is known of the ethanol effects on purinergic receptor-operated channels in neuronal cells.(omitted)

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