The effect of μ-opioid receptor activation on GABAergic neurons in the spinal dorsal horn

Kim, Yoo Rim,Shim, Hyun Geun,Kim, Chang-Eop,Kim, Sang Jeong The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.4

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of ${\mu}$-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective ${\mu}$-opioid agonist, [$D-Ala^2$, $NMe-Phe^4$, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by $K^+$ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

S1 Employs Feature-Dependent Differential Selectivity of Single Cells and Distributed Patterns of Populations to Encode Mechanosensations

Kim, Yoo Rim,Kim, Chang-Eop,Yoon, Heera,Kim, Sun Kwang,Kim, Sang Jeong Frontiers Media S.A. 2019 Frontiers in cellular neuroscience Vol.13 No.-

<P>The primary somatosensory (S1) cortex plays an important role in the perception and discrimination of touch and pain mechanosensations. Conventionally, neurons in the somatosensory system including S1 cortex have been classified into low/high threshold (HT; non-nociceptive/nociceptive) or wide dynamic range (WDR; convergent) neurons by their electrophysiological responses to innocuous brush-stroke and noxious forceps-pinch stimuli. Besides this “noxiousness” (innocuous/noxious) feature, each stimulus also includes other stimulus features: “texture” (brush hairs/forceps-steel arm), “dynamics” (dynamic stroke/static press) and “intensity” (weak/strong). However, it remains unknown how S1 neurons inclusively process such diverse features of brushing and pinch at the single-cell and population levels. Using <I>in vivo</I> two-photon Ca<SUP>2+</SUP> imaging in the layer 2/3 neurons of the mouse S1 cortex, we identified clearly separated response patterns of the S1 neural population with distinct tuning properties of individual cells to texture, dynamics and noxiousness features of cutaneous mechanical stimuli. Among cells other than broadly tuned neurons, the majority of the cells showed a highly selective response to the difference in texture, but low selectivity to the difference in dynamics or noxiousness. Between the two low selectivity features, the difference in dynamics was slightly more specific, yet both could be decoded using the response patterns of neural populations. In addition, more neurons are recruited and stronger Ca<SUP>2+</SUP> responses are evoked as the intensity of forceps-pinch is gradually increased. Our results suggest that S1 neurons encode various features of mechanosensations with feature-dependent differential selectivity of single cells and distributed response patterns of populations. Moreover, we raise a caution about describing neurons by a single stimulus feature ignoring other aspects of the sensory stimuli.</P>

한의학 연구자를 위한 시스템 생물학 학습 가이드

김창업(Chang-Eop Kim) 한의병리학회 2016 동의생리병리학회지 Vol.30 No.6

한의학과 시스템생물학의 만남, 의미와 전망

김창업(Chang-Eop Kim),이충열(Choong Yeol Lee) 한의병리학회 2016 동의생리병리학회지 Vol.30 No.6

The effect of μ-opioid receptor activation on GABAergic neurons in the spinal dorsal horn

Yoo Rim Kim,Hyun Geun Shim,Chang-Eop Kim,Sang Jeong Kim 대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.4

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of μ-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective μ-opioid agonist, [D-Ala2, NMe-Phe4, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by K+ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

Correlation 분석 기법을 적용한 요통 환자에 관한 레지스트리 데이터의 탐색적 분석

박창현,박무순,김형석,차윤엽,김순중,고연석,오민석,황의형,신병철,김창업,송윤경,Park, Chang-Hyun,Park, Mu-Sun,Kim, Hyung-Suk,Cha, Yun-Yeop,Kim, Soon-Joong,Ko, Youn-Suk,Oh, Min-Seok,Hwang, Eui-Hyoung,Shin, Byung-Cheul,Kim, Chang-Eop,Song 한방재활의학과학회 2017 한방재활의학과학회지 Vol.27 No.4

Objectives The aim of this study is to analyze the patients who have low back pain through registry. Methods We registered patients with low back pain who visited department of korean rehabilitation medicine in university hospitals on study. We collected data from 116 subjects consisted of 51 inpatients and 65 outpatients and ruled out 8 who didn't have pattern identification data at the point of inpatient or outpatient visit so we analyzed 108 in total. We used Pearson's product moment correlation to find correlationship among variables, and analyzed statistical data using Phyton scipy library stats package. Results We set general features, region of the pain, physical examination, ROM, questionnaire results, pattern identification as variables and draw a conclusion by analyzing these variables. Conclusions Registry aimed at low back pain patients was established in department of korean rehabilitation medicine of university hospitals and exploratory analysis based on data were made. Through the registry, we expect that more advanced studies will be performed; for example, executing research which verifies effectiveness and stability of korean medical treatment or developing tools to fill the gap between pattern identification and disease identification.

Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions

Kim, Ki Hyun,Lee, Dahae,Lee, Hye Lim,Kim, Chang-Eop,Jung, Kiwon,Kang, Ki Sung The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.3

In recent years, several therapeutic drugs have been rationally designed and synthesized based on the novel knowledge gained from investigating the actions of biologically active chemicals derived from foods, plants, and medicinal herbs. One of the major advantages of these naturalistic chemicals is their ability to interact with multiple targets in the body resulting in a combined beneficial effect. Ginseng is a perennial herb (Araliaceae family), a species within the genus Panax, and a highly valued and popular medicinal plant. Evidence for the medicinal and health benefits of Panax ginseng and its components in preventing neurodegeneration has increased significantly in the past decade. The beneficial effects of P. ginseng on neurodegenerative diseases have been attributed primarily to the antioxidative and immunomodulatory activities of its ginsenoside components. Mechanistic studies on the neuroprotective effects of ginsenosides revealed that they act not only as antioxidants but also as modulators of intracellular neuronal signaling and metabolism, cell survival/death genes, and mitochondrial function. The goal of the present paper is to provide a brief review of recent knowledge and developments concerning the beneficial effects as well as the mechanism of action of P. ginseng and its components in the treatment and prevention of neurodegenerative diseases.

Numerical Analysis on Transport Phenomena of Liquid-Metal in DC EM Pump

GilDong Kim,Jong Hoon Park,Chang Eop Kim,Kyoung Woo Park 호서대학교 공업기술연구소 2015 공업기술연구 논문집 Vol.34 No.1

Recently, the electrom agnetic (EM ) p u m p has been w idely used for cooling th e h ig h th e rm a l power system such as nuclear reactors because it has m an y ad vanta g e of th e lower pressure loss, absence of m oving components, an d allow ance of continuous flu id flow com pared w ith th e conventional m echanical p u m p (i.e., a ce ntrifug al p u m p ). The basic o p eratin g p rin ciple of E M pum ps is th a t in the presence of a n ex ternal m ag ne tic field, the in te ra c tio n betw een the electrical current an d transverse m ag ne tic fields results in Lorentz forces th ro u g h an electrically conducting liq u id m etal. This is th e d o m a in of m agneto-hydrodynam ics (M H D ). In the present study, the tran sp o rt phenom ena in the E M p u m p w hich is formed a rec tang ular chann el are in vestig ated by usin g the C F D technology. As the results of s im u la tio n , the follow ing conclusions are o b ta in e d ; It is found th a t th e typical M -shaped velocity profiles in the chann el for liq u id m etal can be ob tain ed due to th e Lorentz force w hich is produced by bo th the m agnetic field an d current density. The average velocity a n d pressure drop in the E M p u m p chann el are increased, sim ultan e o usly , as th e m ag ne tic field an d curre nt density increase and, in tu rn , more p u m p in g power can be predicted by the influence of them .

잠재적 창업가의 예비 창업행동과 사회적 책임의식 간의 관계: 마이스터고 학생들을 중심으로

김대업 ( Dae Eop Kim ),성창수 ( Chang Soo Sung ) 한국중소기업학회 2013 中小企業硏究 Vol.35 No.1

장기적 경기불황으로 장기적 경기불황으로 인하여 전 세계적으로 실업문제가 주요 이슈가 되고 있는 상황에서 특히 청년실업에 대한 관심이 높아지고 있다. 많은 국가들이 공통적으로 실업문제의 해결 빛 일자리 창출을 위하여 정책적 초점을 청년창업에 두고 있으며 창업관련 교육의 대상이 점차 청소년기의 잠재적 창업자로 확대되고 있다. 이와 더불어 기업들의 사회적 책임에 대한 논의가 활발하게 이루어지고 있다. 청소년기의 잠재적 창업자는 미래의 국가발전 원동력의 원천이며 이들이 창업을 성공하고 성공적인 기업경영을 통하여 성과를 낼 때 개인적인 또는 국가적인 발전이 이루어질 수 있다. 창업관련 많은 연구들도 이러한 점에 맞추어 연구가 진행되어 왔다. 그러나 이는 단순히 경제적인 측면만 고려한 것이고 사회적 측면을 간과하고 있다. 기업에 대한 사회경제적인 관점이 대두되면서 사회구성원으로서 기업의 역할인 사회적 책임이 강조 되고 있으며 주로 대기업의 역할이 이슈화되고 있다. 창업가의 사회적 책임에 대해서는 창업관련 문헌과 기업윤리 문헌에서 제한적으로 다루어져 왔으며 잠재적 창업가들의 창업 이전 실제 행동 역시 최근 들어 연구되기 시작하였다. 지금까지의 창업관련 연구는 창업성과에 초점을 두고 진행되어왔지만 주목해야 할 점은 잠재적 창업가들의 창업성공과 더불어 사회적 책임을 제대로 수행하는 것이 지역사회와 국가발전에 더욱 중요하다는 것이다. 본 연구에서는 청소년기의 잠재적 창업가들이 가지고 있는 창업의도가 실제적인 창업행동에 어떠한 영향을 미치는지, 그리고 창업의도와 창업행동이 창업 이후에 사회적 책임을 어느 정도 수행할 것인지의 사회적 책임의도에 미치는 영향에 초점을 맞추고 있다. 이를 위하여 창업의도모형, 초기 창업가 행동모형, 창업가적 기대모형, 그리고 롤 모델이 고려되었다. 분석결과, 창업의도는 초기 창업가 행동에 유의한 영향을 미쳤으며 사회적 책임의도 또한 유의한 영향을 미쳤다. 그러나 초기 창업가 행동은 사회적 책임의도에 부정적인 영향을 미치는 것으로 나타났다. 선행연구들에서는 잠재적 창업가는 롤 모델에 의하여 많은 영향을 받는다고 설명되고 있으나, 본 연구의 표본에서는 전반적으로 롤 모델에 대한 노출수준이 낮은 것으로 나타났으며 세 가지 인과관계에 조절역할을 미치지 못하는 것으로 나타났다. The long-term economic recession worldwide has brought the unemploy-ment issue into focus, especially the youth unemployment. Some countries in Europe are putting their efforts to broaden the job opportunities for their potential entrepreneurs who are high school students. In addition, the issue of corporate social responsibility has become another hot potato domestically. Potential entrepreneurs in their adolescence are major and potential sources for national development and their successes in businesses are deeply related to the national development So many studies in entrepreneurship have been focused on this. Too much focus on economic aspects, however, has made the social aspects overlooked. As socio-economic view on corporations has emerged, the role of corporate social responsibility as a member of society has been stressed and has become a primary issue in countries. The research on corporate social responsibility has been done limitedly in the fields of entrepreneurship and business ethics. Studies on actual behaviors of potential entrepreneurs have started only recently. Until now, entrepreneur-ship-related studies have been tailored to the success of new venture or start-up business, it should be noted that performing social responsibility as well as entrepreneurial success is more vital to the regional and national development This study focuses on two things. First, how much entrepreneurial intentions of potential entrepreneurs affect their actual entrepreneurial behaviors. Second, how much their entrepreneurial intentions and behaviors affect their social responsibility. For this, entrepreneurial Intention model, entrepreneurial nascent behavior model, entrepreneurial expectation model, and role mode have been considered. Entrepreneurial intention had positive effect on entrepreneurial nascent behavior and intention of social responsibility. Entrepreneurial nascent behavior has negative effect on intention of social responsibility. There are not moderate effects of role model exposure on three causal relationships.

Protective Effect of <i>Artemisia argyi</i> and Its Flavonoid Constituents against Contrast-Induced Cytotoxicity by Iodixanol in LLC-PK1 Cells

Lee, Dahae,Kim, Chang-Eop,Park, Sa-Yoon,Kim, Kem Ok,Hiep, Nguyen Tuan,Lee, Dongho,Jang, Hyuk-Jai,Lee, Jae Wook,Kang, Ki Sung MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.5

<P>Preventive effects and corresponding molecular mechanisms of mugwort (<I>Artemisia argyi</I>) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found that <I>A. argyi</I> extracts ameliorated the reduction in cellular viability following iodixanol treatment. The anti-apoptotic effect of <I>A. argyi</I> extracts on contrast-induced nephrotoxicity was mediated by the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation and the activation of caspases. The flavonoid compounds isolated from <I>A. argyi</I> improved the viability of iodixanol-treated cells against contrast-induced nephrotoxicity. Seven compounds (<B>1</B>, <B>2</B>, <B>3</B>, <B>15</B>, <B>16</B>, <B>18</B>, and <B>19</B>) from 19 flavonoids exerted a significant protective effect. Based on the in silico oral-bioavailability and drug-likeness assessment, which evaluate the drug potential of these compounds, compound <B>2</B> (artemetin) showed the highest oral bioavailability (49.55%) and drug-likeness (0.48) values. We further investigated the compound–target–disease network of compound <B>2</B>, and proliferator-activated receptor gamma (PPAR-γ) emerged as a predicted key marker for the treatment of contrast-induced nephrotoxicity. Consequently, compound <B>2</B> was the preferred candidate, and its protective effect was mediated by inhibiting the contrast-induced inflammatory response through activation of PPAR-γ and inhibition of MAPK phosphorylation and activation of caspases.</P>