• International Journal of Oral Biology
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• v.45 no.4
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• pp.225-231
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• 2020

Glial cells, including astrocytes and microglia, interact closely with neurons and modulate pain transmission, particularly under pathological conditions. In this study, we examined the excitability of substantia gelatinosa (SG) neurons of the spinal dorsal horn using a patch clamp recording to investigate the roles of microglial activation in the nociceptive processes of rats. We used xanthine/xanthine oxidase (X/XO), a generator of superoxide anion (O2·-), to induce a pathological pain condition. X/XO treatment induced an inward current and membrane depolarization. The inward current was significantly inhibited by minocycline, a microglial inhibitor, and fluorocitrate, an astrocyte inhibitor. To examine whether toll-like receptor 4 (TLR4) in microglia was involved in the inward current, we used lipopolysaccharide (LPS), a highly specific TLR4 agonist. The LPS induced inward current, which was decreased by pretreatment with Tak-242, a TLR4-specific inhibitor, and phenyl N-t-butylnitrone, a reactive oxygen species scavenger. The X/XO-induced inward current was also inhibited by pretreatment with Tak-242. These results indicate that the X/XO-induced inward current of SG neurons occurs through activation of TLR4 in microglial cells, suggesting that neuroglial cells modulate the nociceptive process through central sensitization.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.371-376
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• 2017

The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn; MDH) receives direct inputs from small diameter primary afferent fibers that predominantly transmit nociceptive information in the orofacial region. Recent studies indicate that reactive oxygen species (ROS) is involved in persistent pain, primarily through spinal mechanisms. In this study, we aimed to investigate the role of xanthine/xanthine oxidase (X/XO) system, a known generator of superoxide anion ($O_2{^-}$), on membrane excitability in the rat MDH neurons. For this, we used patch clamp recording and confocal imaging. An application of X/XO ($300{\mu}M/30mU$) induced membrane depolarization and inward currents. When slices were pretreated with ROS scavengers, such as phenyl N-tert-butylnitrone (PBN), superoxide dismutase (SOD), and catalase, X/XO-induced responses decreased. Fluorescence intensity in the DCF-DA and DHE-loaded MDH cells increased on the application of X/XO. An anion channel blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), significantly decreased X/XO-induced depolarization. X/XO elicited an inward current associated with a linear current-voltage relationship that reversed near -40 mV. X/XO-induced depolarization reduced in the presence of $La^{3+}$, a nonselective cation channel (NSCC) blocker, and by lowering the external sodium concentration, indicating that membrane depolarization and inward current are induced by influx of $Na^+$ ions. In conclusion, X/XO-induced ROS modulate the membrane excitability of MDH neurons, which was related to the activation of NSCC.

• Toxicological Research
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• v.23 no.1
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• pp.33-38
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• 2007

Zinc is an endogenous transition metal that can be synaptically released during neuronal activity. However, zinc may contribute to the neuropathology associated with a variety of conditions. Carnosine expressed in glial cells can modulate the effects of zinc on neuronal excitability as a zinc chelator. We hypothesize that carnosine may protect against neurotoxicity of zinc in cortical neuronal cells. The cortical neuronal cells from newborn rats were prepared and exposed to zinc chloride and/or carnosine at various concentrations. Zinc at the doses of 0 to $500{\mu}M$ decreased neuronal cell viability in a dose-dependent manner. Additionally, at the concentrations of 100 and $200{\mu}M$, it significantly decreased cell viability in an exposed time-dependent manner (p < 0.05). Treatment with carnosine at the concentrations of 20 and $200{\mu}M$ significantly increased neuronal cell proliferation by approximately 14% and 20%, respectively, compared to the control (p < 0.05). At the concentrations of 100 and $200{\mu}M$ zinc, $20{\mu}M$ carnosine significantly increased the viability of neuronal cells by 18.3% and 12.1 %, and $200{\mu}M$ carnosine also increased it by 33.5% and 28.6%, respectively, compared to the normal control group (p < 0.01). These results suggest that carnosine at a physiologically relevant level may protect against zinc-mediated toxicity in neuronal cells as an endogenous neuroprotective agent.

• Journal of Ginseng Research
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• v.21 no.1
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• pp.1-12
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• 1997

Ginseng, the root of Panax ginseng C.A. Meyer, is well-known oriental herbal medicine. The number of paper reporting the effects on its physiological, pharmacological, and behavioral effects has been increased every year, since ginsenosides isolated from ginseng are known to be biologically active components. This brief review summarizes some of new findings from recently published papers on ginsenosides or ginseng saponins. Therefore, this paper includes the various effects of ginsenosides on neuronal cell growths, on behavior of experimental animals, on enzyme activities, on the release and uptake of neurotransmitters, on neuronal cell excitability, on the motility of intestine, on antitumor activity, on cardiovascular system and metabolism. In spite of various effects of ginsenosides on various cells or organs, it is still to date impossible for one to clearly explain the exact mechanism on the action of ginsenosides. However, in this article I will discuss several papers providing possible explanations on the physiological and pharmacological actions including signal transudation pathway of ginsenosides. The elucidation of the exact mechanism of ginsenosides on cellular or molecular level will not only give us a chance to explain why people have used ginseng as an elixir of life for several thousands of year but also give us a crucial chance to apply ginseng to modern medicine.

• Journal of Medicine and Life Science
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• v.15 no.2
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• pp.62-66
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• 2018

A-type $K^+$ ($I_A$) channels are transiently activated in the suprathreshold membrane potential and then rapidly inactivated. These channels play roles to control the neuronal excitability in pyramidal neurons in hippocampi. We here electrophysiologically tested if regulatory functions of $I_A$ channels might be targeted by acute activation of glutamatergic synaptic transmission in cultured hippocampal neurons(DIV 6~8). The application of high KCl in recording solutions(10 mM, 2 min) to increase presynaptic glutamate release, significantly reduced the peak of somatic $I_A$ without changes of gating kinetics. This indicates that neuronal excitation induced by the enhancement of synaptic transmission may process with distinctive signaling cascades to affect voltage-dependent ion channels in hippocampal neurons. Therefore, it is possible that short-lasting enhancement of synaptic transmission is functionally restricted in local synapses without effects on intracellular signaling cascades affecting a whole neuron, efficiently and rapidly enhancing synaptic functions in hippocampal network.

• Journal of The Korean Society of Clinical Toxicology
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• v.17 no.2
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• pp.66-78
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• 2019

Purpose: Thallium (TI+) autometallography is often used for the imaging of neuronal metabolic activity in the rodent brain under various pathophysiologic conditions. The purpose of this study was to apply a thallium autometallographic technique to observe changes in neuronal activity in the forebrain of rats following acute carbon monoxide (CO) intoxication. Methods: In order to induce acute CO intoxication, adult Sprague-Dawley rats were exposed to 1100 ppm of CO for 40 minutes, followed by 3000 ppm of CO for 20 minutes. Animals were sacrificed at 30 minutes and 5 days after induction of acute CO intoxication for thallium autometallography. Immunohistochemical staining and toluidine blue staining were performed to observe cellular damage in the forebrain following intoxication. Results: Acute CO intoxication resulted in significant reduction of TI+ uptake in major forebrain structures, including the cortex, hippocampus, thalamus, and striatum. In the cortex and hippocampal CA1 area, marked reduction of TI+ uptake was observed in the cell bodies and dendrites of pyramidal neurons at 30 minutes following acute CO intoxication. There was also strong uptake of TI+ in astrocytes in the hippocampal CA3 area following acute CO intoxication. However, there were no significant histological findings of cell death and no reduction of NeuN (+) neuronal populations in the cortex and hippocampus at 5 days after acute CO intoxication. Conclusion: The results of this study suggest that thallium autometallography can be a new and useful technique for imaging functional changes in neural activity of the forebrain structure following mild to moderate CO intoxication.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.285-289
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• 2014

Transcranial magnetic stimulation (TMS) is a noninvasive and safe technique for motor cortex stimulation. TMS is used to treat neurological and psychiatric disorders, including mood and movement disorders. TMS can also treat several types of chronic neuropathic pain. The pain relief mechanism of cortical stimulation is caused by modifications in neuronal excitability. Depression is a common co-morbidity with chronic pain. Pain and depression should be treated concurrently to achieve a positive outcome. Insomnia also frequently occurs with chronic lower back pain. Several studies have proposed hypotheses for TMS pain management. Herein, we report two cases with positive results for the treatment of depression and insomnia with chronic low back pain by TMS.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.215-219
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• 2007

Small and large conductance $Ca^{2+}$-activated $K^+(SK_{Ca}\;and\;BK_{Ca})$ channels are implicated in the modulation of neuronal excitability. We investigated how changes in peripheral $K_{Ca}$ channel activity affect mechanical sensitivity as well as the afferent fiber type responsible for $K_{Ca}$ channel-induced mechanical sensitivity. Blockade of $SK_{Ca}$ and $BK_{Ca}$ channels induced a sustained decrease of mechanical threshold which was significantly attenuated by topical application of capsaicin onto afferent fiber and intraplantar injection of 1-ethyl-2-benzimidazolinone. NS1619 selectively attenuated the decrease of mechanical threshold induced by charybdotoxin, but not by apamin. Spontaneous flinching and paw thickness were not significantly different after $K_{Ca}$ channel blockade. These results suggest that mechanical sensitivity can be modulated by $K_{Ca}$ channels on capsaicin-sensitive afferent fibers.

• Research in Vestibular Science
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• v.17 no.4
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• pp.142-151
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• 2018

Objectives: Excitability o medial vestibular nucleus (MVN) in the brainstem can be affected by changes in the arterial blood pressure. Several animal studies have demonstrated that acute hypotension results in the alteration of multiunit activities and expression of cFos protein in the MVN. In the field of extracellular electrophysiological recording, tetrode technology and spike sorting algorithms can easily identify single unit activity from multiunit activities in the brain. However, detailed properties of electrophysiological changes in single unit of the MVN during acute hypotension have been unknown. Methods: Therefore, we applied tetrode techniques and electrophysiological characterization methods to know the effect of acute hypotension on single unit activities of the MVN of rats. Results: Two or 3 types of unit could be classified according to the morphology of spikes and firing properties of neurons. Acute hypotension elicited 4 types of changes in spontaneous firing of single unit in the MVN. Most of these neurons showed excitatory responses for about within 1 minute after the induction of acute hypotension and then returned to the baseline activity 10 minutes after the injection of sodium nitroprusside. There was also gradual increase in spontaneous firing in some units. In contrast small proportion of units showed rapid reduction of firing rate just after acute hypotension. Conclusions: Therefore, application of tetrode technology and spike sorting algorithms is another method for the monitoring of electrical activity of vestibular nuclear during acute hypotension.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.405-409
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• 2013

We studied the sex different nicotine effect on evoked population spike amplitudes (ePSA) and connexin (Cx) expression in the hippocampus CA1 area of gerbils. Acute doses of nicotine bitartrate (0.5 mg/kg: NT-0.5) slightly reduced ePSA in males but markedly augmented that in females. Acute NT (5.0 mg/kg) markedly increased the ePSA in all gerbils. Unlike acute NT-0.5, repeated NT-0.5 injection (twice a day for 7 days) significantly increased the ePSA in males and slightly affected the NT-0.5 effect in females. The Cx36 and Cx43 expression levels as well as Cx expressing neuronal populations were significantly increased by repeated NT-0.5 in in both male and female gerbils, and particularly, Cx43 expression was somewhat prominent in females. These results demonstrated a sex difference with respect to the nicotine effect on hippocampal bisynaptic excitability, irrelevant to connexin expression.