• Title/Summary/Keyword: Functional neuron

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Ginsenosides Inhibit NMDA Receptor-Mediated Epileptic Discharges in Cultured Hippocampal Neurons

  • Kim, Sun-Oh;Rhim, Hye-Whon
    • Archives of Pharmacal Research
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    • v.27 no.5
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    • pp.524-530
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    • 2004
  • Epilepsy or the occurrence of spontaneous recurrent epileptiform discharges (SREDs, seizures) is one of the most common neurological disorders. Shift in the balance of brain between excitatory and inhibitory functions due to different types of structural or functional alterations may cause epileptiform discharges. N-Methyl-D-aspartate (NMDA) receptor dysfunctions have been implicated in modulating seizure activities. Seizures and epilepsy are clearly dependent on elevated intracellular calcium concentration ([C $a^{2+}$]$_{i}$ ) by NMDA receptor activation and can be prevented by NMDA antagonists. This perturbed [C $a^{2+}$]$_{i}$ levels is forerunner of neuronal death. However, therapeutic tools of elevated [C $a^{2+}$]$_{i}$ level during status epilepticus (SE) and SREDs have not been discovered yet. Our previous study showed fast inhibition of ginseng total saponins and ginsenoside R $g_3$ on NMDA receptor-mediated [C $a^{2+}$]$_{i}$ in cultured hippocampal neurons. We, therefore, examined the direct modulation of ginseng on hippocampal neuronal culture model of epilepsy using fura-2-based digital $Ca^{2+}$ imaging and neuronal viability assays. We found that ginseng total saponins and ginsenoside R $g_3$ inhibited $Mg^{2+}$ free-induced increase of [C $a^{2+}$]$_{i}$ and spontaneous [C $a^{2+}$]$_{i}$ oscillations in cultured rat hippocampal neurons. These results suggest that ginseng may playa neuroprotective role in perturbed homeostasis of [C $a^{2+}$]$_{i}$ and neuronal cell death via the inhibition of NMDA receptor-induced SE or SREDs.d SE or SREDs..

Korean Red Ginseng Extract Activates Non-NMDA Glutamate and GABAA Receptors on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice

  • Yin, Hua;Park, Seon-Ah;Park, Soo-Joung;Han, Seong-Kyu
    • Journal of Ginseng Research
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    • v.35 no.2
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    • pp.219-225
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    • 2011
  • Korean red ginseng (KRG) is a valuable and important traditional medicine in East Asian countries and is currently used extensively for botanical products in the world. KRG has both stimulatory and inhibitory effects on the central nervous system (CNS) suggesting its complicated action mechanisms. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Some studies reported that KRG has antinociceptive effects, but there are few reports of the functional studies of KRG on the SG neurons of the Vc. In this study, a whole cell patch clamp study was performed to examine the action mechanism of a KRG extract on the SG neurons of the Vc from juvenile mice. KRG induced short-lived and repeatable inward currents on all the SG neurons tested in the high chloride pipette solution. The KRG-induced inward currents were concentration dependent and were maintained in the presence of tetrodotoxin, a voltage gated $Na^+$ channel blocker. The KRG-induced inward currents were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and/or picrotoxin, a gamma-aminobutyric acid $(GABA)_A$ receptor antagonist. However, the inward currents were not suppressed by d,l-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. These results show that KRG has excitatory effects on the SG neurons of the Vc via the activation of non-NMDA glutamate receptor as well as an inhibitory effect by activation of the $GABA_A$ receptor, indicating the KRG has both stimulatory and inhibitory effects on the CNS. In addition, KRG may be a potential target for modulating orofacial pain processing.

Upregulation of Dendritic Arborization by N-acetyl-D-Glucosamine Kinase Is Not Dependent on Its Kinase Activity

  • Lee, HyunSook;Dutta, Samikshan;Moon, Il Soo
    • Molecules and Cells
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    • v.37 no.4
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    • pp.322-329
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    • 2014
  • N-acetylglucosamine kinase (GlcNAc kinase or NAGK; EC 2.7.1.59) is highly expressed and plays a critical role in the development of dendrites in brain neurons. In this study, the authors conducted structure-function analysis to verify the previously proposed 3D model structure of GlcNAc/ATP-bound NAGK. Three point NAGK mutants with different substrate binding capacities and reaction velocities were produced. Wild-type (WT) NAGK showed strong substrate preference for GlcNAc. Conversion of Cys143, which does not make direct hydrogen bonds with GlcNAc, to Ser (i.e., C143S) had the least affect on the enzymatic activity of NAGK. Conversion of Asn36, which plays a role in domain closure by making a hydrogen bond with GlcNAc, to Ala (i.e., N36A) mildly reduced NAGK enzyme activity. Conversion of Asp107, which makes hydrogen bonds with GlcNAc and would act as a proton acceptor during nucleophilic attack on the ${\gamma}$-phosphate of ATP, to Ala (i.e., D107A), caused a total loss in enzyme activity. The overexpression of EGFP-tagged WT or any of the mutant NAGKs in rat hippocampal neurons (DIV 5-9) increased dendritic architectural complexity. Finally, the overexpression of the small, but not of the large, domain of NAGK resulted in dendrite degeneration. Our data show the effect of structure on the functional aspects of NAGK, and in particular, that the small domain of NAGK, and not its NAGK kinase activity, plays a critical role in the upregulation of dendritogenesis.

Impaired Taste Associative Memory and Memory Enhancement by Feeding Omija in Parkinson's Disease Fly Model

  • Poudel, Seeta;Lee, Youngseok
    • Molecules and Cells
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    • v.41 no.7
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    • pp.646-652
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    • 2018
  • Neurodegeneration can result in memory loss in the central nervous system (CNS) and impairment of taste and smell in the peripheral nervous system (PNS). The neurodegeneration seen in Parkinson's disease (PD) is characterized by functional loss of dopaminergic neurons. Recent studies have also found a role for dopaminergic neurons in regulating taste memory rewards in insects. To investigate how taste memories and sugar sensitivity can be affected in PD, we utilized the $DJ-1{\beta}$ mutant fruit fly, $DJ-1{\beta}^{ex54}$, as a PD model. We performed binary choice feeding assays, electrophysiology and taste-mediated memory tests to explore the function of the $DJ-1{\beta}$ gene in terms of sugar sensitivity as well as associative taste memory. We found that PD flies exhibited an impaired ability to discriminate sucrose across a range of sugar concentrations, with normal responses at only very high concentrations of sugar. They also showed an impairment in associative taste memory. We highlight that the taste impairment and memory defect in $DJ-1{\beta}^{ex54}$ can be recovered by the expression of wild-type $DJ-1{\beta}$ gene in the dopaminergic neurons. We also emphasized the role of dopaminergic neurons in restoring taste memory function. This impaired memory property of $DJ-1{\beta}^{ex54}$ flies also allows them to be used as a model system for finding supplementary dietary foods that can improve memory function. Here we provide evidence that the associative taste memory of both control and $DJ-1{\beta}^{ex54}$ flies can be enhanced with dietary supplementation of the medicinal plant, omija.

Neural network analysis using neuralnet in R (R의 neuralnet을 활용한 신경망분석)

  • Baik, Jaiwook
    • Industry Promotion Research
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    • v.6 no.1
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    • pp.1-7
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    • 2021
  • We investigated multi-layer perceptrons and supervised learning algorithms, and also examined how to model functional relationships between covariates and response variables using a package called neuralnet. The algorithm applied in this paper is characterized by continuous adjustment of the weights, which are parameters to minimize the error function based on the comparison between the actual and predicted values of the response variable. In the neuralnet package, the activation and error functions can be appropriately selected according to the given situation, and the remaining parameters can be set as default values. As a result of using the neuralnet package for the infertility data, we found that age has little influence on infertility among the four independent variables. In addition, the weight of the neural network takes various values from -751.6 to 7.25, and the intercepts of the first hidden layer are -92.6 and 7.25, and the weights for the covariates age, parity, induced, and spontaneous to the first hidden neuron are identified as 3.17, -5.20, -36.82, and -751.6.

The Effect of Action Observation Training on Upper Motor Function in Stroke Patients : A Multiple Bbaseline Design (동작관찰훈련이 뇌졸중 환자의 상지운동기능에 미치는 영향 : 다중기초선연구)

  • Yun, Tae-Won;Park, Hye-Ryoung;Kim, Tae-Yoon;Lee, Moon-Kyu
    • PNF and Movement
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    • v.12 no.2
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    • pp.123-132
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    • 2014
  • Purpose: The discovery of mirror neuron system may positively affect functional recovery; therefore, rehabilitation is needed that is practical for use in clinical settings. The purpose of this study was to examine the effect of action observation training on upper motor function in people who had suffered strokes. Methods: Three elderly patients with stroke, aged to years, were recruited from a stroke rehabilitation center. A nonconcurrent, multiple baseline subject approach was taken, with an A-B-A treatment single-subject experimental design, and the experiment was conducted for 3 weeks. The action observation training was repeated 5 times in 5 days during the intervention period. The arm function, including WMFT, BBT, and grip and pinch strength, was evaluated in each subject 5 times during the baseline period, the intervention period, and the baseline regression period. Results: The results of the evaluation for each subject were presented as mean values and video graphs. The WMFT scores of 2 subjects were improved during the intervention period in comparison with the baseline period, and this improvement was maintained even during the regression baseline period. The BBT and the grip and pinch strength were not improved. Conclusion: Based on these results, we suggest that the action observation training for 5 sessions was effective in improving upper limb function of stroke patients but was not effective in improving hand dexterity or grip and pinch strength.

Enhanced Expression of Phospholipase C-$\gamma$1 in Regenerating Murine Neuronal Cells by Pulsing Electromagnetic Field (흰쥐에서 편측 반회후두신경 재지배 후 Phopholipase C-$\gamma$1(PLC-$\gamma$1)의 발현과 후두기능회복과의 관계)

  • 정성민;신혜정;김성숙;김문정;윤선옥;박수경;신유리;김진경
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.12 no.2
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    • pp.126-132
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    • 2001
  • Background and Objectives : Signal traduction through phospholipase C(PLC) participate in the regulation of cell growth and differentiation. Growth factors bind to their receptors and thereby induce tyrosine phophorylation of the phospholipase C-${\gamma}$1(PLC-${\gamma}$1). PLC-${\gamma}$1 is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. Tyrosine kinase phosphorylation of PLC-${\gamma}$1 stimulates PLC activation and cell proliferation. However the signal transduction pathway and the significance of PLC in injured recurrent laryngeal nerve regeneration is unknown. Therefore after we obtained fuctionally recovered rats using PEMF in this study, we attempt to provide some evidence that PLC plays a role in nerve regeneration itself and regeneration related to PEMF through the analysis of the difference between fucntional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 32 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The experimental group(n=16) received PEMS by placing them in custom cages equipped with Helm-holz coils(3hr/day, 5days/wk, for 12wk). The control group(n=16) were handled the same way as the experimental group, except that they did not receive PEMS. Laryngo-videoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining and Western blotting analysis using monoclonal antibody was performed to detect PLC-${\gamma}$1 in recurrent laryngeal nerve and nodose ganglion. Results : 10 rats(71%) in experimental group and 4 rats(38%) in the control group showed recovery of vocal fold motion. Functionally-recoverd rats show PLC-${\gamma}$1 positive cells in neuron and ganglion cells after 12 weeks from nerve injury. Conclusion : This study shows that PLC1-${\gamma}$ involved in singnal trasduction pathway in functinal recovery of injured recurrent laryngeal nerve and PEMF enhance the functional recovery by effect on this molecule.

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Effect of Stem Cell Transplantation on Pain Behavior and Locomotor Function in Spinal Cord Contusion Model

  • Park, Hea-Woon;Kim, Su-Jeong;Cho, Yun-Woo;Hwang, Se-Jin;Lee, Won-Yub;Ahn, Sang-Ho;Jang, Sung-Ho
    • The Journal of Korean Physical Therapy
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    • v.22 no.3
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    • pp.79-85
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    • 2010
  • Purpose: Many trials for new therapeutic approaches such as stem cell-based transplantation have been conducted to improve the repair and regeneration of injured cord tissue and to restore functions following spinal cord injury (SCI) in animals and humans. Adipose tissue-derived stromal cells (ATSCs) have multi-lineage potential to differentiate into cells with neuron-like morphology. Most studies of stem cell transplantation therapy after SCI are focused on cellular regeneration and restoration of motor function, but not on unwanted effects after transplantation such as neuropathic pain. This study was focused on whether transplantation of ATSCs could facilitate or attenuate hindpaw pain responses to heat, cold and mechanical stimulation, as well as on improvement of locomotor function in a rat with SCI. Methods: A spinal cord injury rat model was produced using an NYU impactor by dropping a 10 g rod from a height of 25 mm on to the T9 segment. Human ATSCs (hATSCs; approximately $5{\times}10^5$ cells) or DMEM were injected into the perilesional area 9 days after the SCI. After transplantation, hindpaw withdrawal responses to heat, cold and mechanical allodynia were measured over 7 weeks. Motor recovery on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and on the inclined plane test were also evaluated. Results: The present study demonstrated that increased hindpaw withdrawal responses to cold allodynia was observed in both groups after transplantation, but the development of cold-induced allodynia in the hATSC transplantation group was significantly larger than in the control group. The difference between the two groups in locomotor functional improvement after SCI was also significant. Conclusion: Careful consideration not only of optimal functional benefits but also of unintended side effects such as neuropathic pain is necessary before stem cell transplantation therapy after SCI.

Lower Motor Weakness and Complex Regional Pain Syndrome of Lower Limb in the Patient of Frontotemporal Dementia: A Case Report (이마관자엽 치매 환자에서 나타난 하지 근력 저하와 복합부위 통증증후군에 대한 증례 보고)

  • Lee, Kwang Min;Noh, Se Eung;Joo, Min Cheol;Hwang, Yong;Kim, Ji Hee
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.12
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    • pp.352-358
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    • 2017
  • Frontotemporal dementia, the second most common cause of early onset dementia, is a neurodegenerative clinical syndrome characterized by progressive deficits in behavior, executive function and language. Although motor symptoms in frontotemporal dementia are represented by motor neuron disease, parkinsonism and progressive supranuclear palsy syndrome, there have been no reports of motor weakness caused by the direct involvement of central motor nervous systems in frontotemporal dementia. Moreover, no association between clinical dementia groups and complex regional pain syndrome has been reported. We diagnosed a rare case with motor weakness and complex regional pain syndrome of lower limbs due to central nervous system lesion in a patient with frontotemporal dementia by magnetic resonance imaging, electrodiagnostic study and three phase bone scan. Following steroid therapy for complex regional pain syndrome, pain was improved. Functional improvement was noted after rehabilitation therapy, including functional electrical stimulation, muscle strengthening exercise and gait training during hospitalization. This case report suggests that rehabilitation therapy for motor weakness in frontotemporal dementia could be effective for improving overall function.

Protective effects of red ginseng treated with gold nanoparticles against H2O2-induced oxidative stress in neuronal PC-12 cells (금 나노입자를 처리한 홍삼의 산화스트레스 완화 및 PC-12 신경세포 보호)

  • Kim, Ji Won;Cho, Chi Heung;Hwang, Yun-Gu;Park, Woo Jung;Kang, Hee;Kim, Dae-Ok
    • Korean Journal of Food Science and Technology
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    • v.49 no.2
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    • pp.222-227
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    • 2017
  • Red ginseng prepared from fresh 6-year-old ginseng treated with colloidal gold nanoparticles was extracted using hot water to evaluate its total phenolic and flavonoid contents, antioxidant capacity, and neuroprotective effects. Water extract of red ginseng treated with gold nanoparticles (WERGGN) had total phenolic and total flavonoid contents of 212.2 mg gallic acid equivalents/$^{\circ}Bx$ and 3.5 mg catechin equivalents/$^{\circ}Bx$, respectively. The antioxidant capacities of WERGGN measured using ABTS, DPPH, and ORAC assays were 272.3, 141.2, and 868.4 mg vitamin C equivalents/$^{\circ}Bx$, respectively. The WERGGN showed protective effects on the viability of neuron-like PC-12 cells against oxidative stress induced by hydrogen peroxide in a dose-dependent manner, partly because of a reduction in intracellular oxidative stress. Acetylcholinesterase and butyrylcholinesterase, which degrade the neurotransmitter acetylcholine to terminate neurotransmission, were inhibited by treatment with WERGGN. These results suggest that WERGGN is useful as a functional material to decrease oxidative stress and neuronal damage.