• The Korean Journal of Physiology and Pharmacology
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• 제17권4호
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• pp.299-306
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• 2013

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been widely used as a treatment for the movement disturbances caused by Parkinson's disease (PD). Despite successful application of DBS, its mechanism of therapeutic effect is not clearly understood. Because PD results from the degeneration of dopamine neurons that affect the basal ganglia (BG) network, investigation of neuronal responses of BG neurons during STN DBS can provide informative insights for the understanding of the mechanism of therapeutic effect. However, it is difficult to observe neuronal activity during DBS because of large stimulation artifacts. Here, we report the observation of neuronal activities of the globus pallidus (GP) in normal and PD model rats during electrical stimulation of the STN. A custom artifact removal technique was devised to enable monitoring of neural activity during stimulation. We investigated how GP neurons responded to STN stimulation at various stimulation frequencies (10, 50, 90 and 130 Hz). It was observed that activities of GP neurons were modulated by stimulation frequency of the STN and significantly inhibited by high frequency stimulation above 50 Hz. These findings suggest that GP neuronal activity is effectively modulated by STN stimulation and strongly dependent on the frequency of stimulation.

• Journal of Microbiology and Biotechnology
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• 제27권6호
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• pp.1163-1170
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• 2017

Clostridium difficile releases two exotoxins, toxin A and toxin B, which disrupt the epithelial cell barrier in the gut to increase mucosal permeability and trigger inflammation with severe diarrhea. Many studies have suggested that enteric nerves are also directly involved in the progression of this toxin-mediated inflammation and diarrhea. C. difficile toxin A is known to enhance neurotransmitter secretion, increase gut motility, and suppress sympathetic neurotransmission in the guinea pig colitis model. Although previous studies have examined the pathophysiological role of enteric nerves in gut inflammation, the direct effect of toxins on neuronal cells and the molecular mechanisms underlying toxin-induced neuronal stress remained to be unveiled. Here, we examined the toxicity of C. difficile toxin A against neuronal cells (SH-SY5Y). We found that toxin A treatment time- and dose-dependently decreased cell viability and triggered apoptosis accompanied by caspase-3 activation in this cell line. These effects were found to depend on the up-regulation of reactive oxygen species (ROS) and the subsequent activation of p38 MAPK and induction of $p21^{Cip1/Waf1}$. Moreover, the N-acetyl-$\text\tiny L$-cysteine (NAC)-induced down-regulation of ROS could recover the viability loss and apoptosis of toxin A-treated neuronal cells. These results collectively suggest that C. difficile toxin A is toxic for neuronal cells, and that this is associated with rapid ROS generation and subsequent p38 MAPK activation and $p21^{Cip1/Waf1}$ up-regulation. Moreover, our data suggest that NAC could inhibit the toxicity of C. difficile toxin A toward enteric neurons.

• 한국융합학회논문지
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• 제7권2호
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• pp.61-67
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• 2016

후각기관은 주변 환경의 다양한 화학물질을 감지하는 기관으로 생존, 종족번식에서 감정에 이르기까지 다양하고 중요한 역할을 하고 있다. 유전적, 환경적 등 다양한 요소에 의해 후각장애가 발생할 수 있으며, 일시적인 경우에는 약물치료 등으로 회복될 수 있지만, 신경세포에 문제가 생긴 영구적인 손상의 경우는 치료가 어렵다. 따라서, 신경세포의 사멸을 억제하거나 재생을 유도하는 치료제의 개발이 필요하다. 본 연구에서는 후각신경세포 특이적으로 GFP 형광단백질을 발현하는 형질전환동물을 제작하여 생체 내 후각신경세포를 관찰하고자 하였다. 또한, 다양한 화학물질을 처리하여 후각신경세포 손상을 인위적으로 유도할 수 있는 방법을 고안하였고, 후각신경세포의 손상 및 재생 과정을 실시간으로 모니터링하였다. 본 연구를 통해 확립된 후각신경세포의 손상 및 재생 모니터링 시스템은 향후 후각신경세포 재생 메커니즘 연구 및 치료제 개발에 유용하게 사용될 것으로 기대된다.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.196.2-197
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• 2003

Parkinson's disease (PO) is a widespread neurodegenerative disorder. Even though PD has been studied in many aspects, it is still unknown the molecular signaling mechanisms linking reactive oxygen species (ROS) and neuronal apoptosis in PD. A better understanding of cellular mechanisms that occur in Parkinson's disease is essential for development of new therapies. In this study we investigated the signaling molecules involved in neuronal apoptosis induced by 6-hydroxydopamine (6-OHDA) in human SK-N-SH neuroblastoma cells as a model cellular system. (omitted)

• 한국지능시스템학회:학술대회논문집
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• 한국퍼지및지능시스템학회 2004년도 춘계학술대회 학술발표 논문집 제14권 제1호
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• pp.277-280
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• 2004

In the research of biomechanical engineering, robotics and neurophysiology, to clarify the mechanism of human bipedal walking is of major interest. It serves as a basis of developing several applications such as rehabilitation tools and humanoid robots Nevertheless, because of complexity of the neuronal system that Interacts with the body dynamics system to make walking movements, much is left unknown about the details of locomotion mechanism. Researchers were looking for the optimal model of the neuronal system by trials and errors. In this paper, we applied Genetic Programming to induce the model of the nervous system automatically and showed its effectiveness by simulating a human bipedal walking with the obtained model.

• 대한의용생체공학회:의공학회지
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• 제17권1호
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• pp.79-84
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• 1996

A number of experimental evidences suggest that the rnun ventrolateral medulla(RVLM) is the final common pathway in the regulation of arterial blood pressure. A Voup of neurons in the RVLM, called the cardiovascular neurons (UN), show spontaneous activity temporally synchronized with the periodic cardiac cycle. These neurons affect the sympathetic nerve discharge(SND), thus are believed to be responsible for blood pressure control. The present experiment identified 98 UVNs in 42 cats based on the temporal relationships between each neuron's activity with both the cardiac cycle and SWD. In 20 UWL changes of spontaneous firing rate(FR) during the somatosympathetic reflex(SSR) were studied Five different firing patterns were observed during the pressor and depressor responses of SSR, implying that they form an interconnected neuronal circuit interacting with one another to generate efferent signals for blood pressure regulation. In the following companion paper, the firing patterns of CVN are analyzed to develop a minimal neuronal circuit model explaining the present experimental outcome.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.21-30
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• 1998

Ginseng root has been considered to prevent neuronal degeneration associated with brain ischemia, but experimental proof in support of this speculation is limited. Moreover, few studies have compared the neuroprotective actions of ginseng ingredients with those of peptide growth factors and cytokines isf vivo. Using a gerbil forebrain ischemia model, we demonstrated that the oral administration of red ginseng powder before an ischemic insult prevents delayed neuronal death in the hippocampal CAI field and that a neuroprotective molecule within red ginseng powder is ginsenoside Rbl. The neurotrophic effect of ginsenoside Rbl, when examined in the gerbil ischemia model and in neuronal cultures was as potent as or more potent than the effects of epidermal growth factor, ciliary neurotrophic factor, erythropoietin, prosaposin, interleukin-6 and interleukin-3. Besides the protection of hippocampal CAI neurons against brain ischemia/repercussion injuries, ginsenoside Rbl was shown to prevent place navigation disability, cortical infarction and secondary thalamic degeneration in stroke-prone spontaneous hypertensive rats with permanent occlusion of the unilateral middle cerebral artery distal to the striate branches. These findings may validate the empirical use of ginseng root for the treatment of cerebrovascular diseases

• The Korean Journal of Physiology and Pharmacology
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• 제10권3호
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• pp.111-121
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• 2006

Neuroprotective properties of lithium were evaluated by using in vivo NMDA excitotoxicity model. Systemic injection of NMDA to young mice induced neuronal apoptosis mediated by both TNFR-l and Fas ligand, and long-term lithium treatment showed noticeable neuroprotection against NMDA-induced excitotoxicity: NMDA-damaged neurons expressed several apoptosis-related gene products such as TNFR-l, Fas ligand, and caspase-3, and these gene expressions were not found in the brain of mice chronically treated with lithium. Therefore, it is highly likely that the protection offered by chronic lithium treatment occurred at far upstream of caspase activation, since the chronic lithium treatment increased the expression of Bcl-2, an important antiapoptotic gene known to act upstream of caspase cascade. Timm's histochemistry indicated the complete blockade of the NMDA insults by the treatment. There was no indication of axonal regeneration, which follows synaptic degeneration induced by neuronal damage. Furthermore, this study reports for the first time that TNFR-l and Fas ligand are involved in neuroprotective effects of lithium in NMDA-induced neuronal apoptosis.

• 대한한의학회지
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• 제26권4호
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• pp.98-107
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• 2005

Objectives: Acupuncture treatment has been clinically used for functional recovery in Parkinson's disease. In the present study, we investigated the effect of acupuncture at Zusanli (ST36) on nigrostriatal dopaminergic neuronal cell death in rats. Methods: A Parkinson's disease model was induced by the unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum. Acupuncture treatment was performed at Zusanli (ST36) and at the hip, as a non-acupoint, once a day for 14 days. Two weeks after 6-0HDA injection, an apomorphine-induced rotational behavior test showed significant rotational asymmetry in rats with Parkinson's disease. Immunostaining for tyrosine hydroxylase demonstrated a dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. Results: Acupuncture at the ST36 acupoint significantly inhibited rotational asymmetry in rats with Parkinson's disease, and also protected against 6-OHDA-induced nigrostriatal dopaminergic neuronal loss. These effects of acupuncture were not observed for non-acupoint acupuncture. Conclusions: The present study shows that acupuncture treatment, especially at the ST36 acupoint, can be used as a useful strategy for the treatment of Parkinson's disease.

• Journal of Ginseng Research
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• 제39권2호
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• pp.148-154
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• 2015

Background: Ginseng is known to have antiapoptotic, anti-inflammatory, and antioxidant effects. The present study investigated a possible role of Korean Red Ginseng (KRG) in suppressing dopaminergic neuronal cell death and the cleavage of p35 to p25 in the substantia nigra (SN) and striatum (ST) using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Methods: Ten-week-old male C57BL/6 mice were injected intraperitoneally with 30 mg/kg of MPTP at 24-h intervals for 5 d, and then administered KRG (1 mg/kg, 10 mg/kg, or 100 mg/kg) once a day for 12 consecutive days from the first injection. Pole tests were performed to assess the motor function of the mice, dopaminergic neuronal survival in the SN and ST was evaluated using tyrosine hydroxylase-immunohistochemistry, and the expressions of cyclin-dependent kinase 5 (Cdk5), p35, and p25 in the SN and ST were measured using Western blotting. Results: MPTP administration caused behavioral impairment, dopaminergic neuronal death, increased Cdk5 and p25 expression, and decreased p35 expression in the nigrostriatal system of mice, whereas KRG dose-dependently alleviated these MPTP-induced changes. Conclusion: These results indicate that KRG can inhibit MPTP-induced dopaminergic neuronal death and suppress the cleavage of p35 to p25 in the SN and the ST, suggesting a possible role for KRG in the treatment of Parkinson's disease.