• Biomolecules & Therapeutics
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• 제21권2호
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• pp.107-113
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• 2013

Plasminogen activator inhibitor-1 (PAI-1) is a member of serine protease inhibitor family, which regulates the activity of tissue plasminogen activator (tPA). In CNS, tPA/PAI-1 activity is involved in the regulation of a variety of cellular processes such as neuronal development, synaptic plasticity and cell survival. To gain a more insights into the regulatory mechanism modulating tPA/PAI-1 activity in brain, we investigated the effects of proteasome inhibitors on tPA/PAI-1 expression and activity in rat primary astrocytes, the major cell type expressing both tPA and PAI-1. We found that submicromolar concentration of MG132, a cell permeable peptide-aldehyde inhibitor of ubiquitin proteasome pathway selectively upregulates PAI-1 expression. Upregulation of PAI-1 mRNA as well as increased PAI-1 promoter reporter activity suggested that MG132 transcriptionally increased PAI-1 expression. The induction of PAI-1 downregulated tPA activity in rat primary astrocytes. Another proteasome inhibitor lactacystin similarly increased the expression of PAI-1 in rat primary astrocytes. MG132 activated MAPK pathways as well as PI3K/Akt pathways. Inhibitors of these signaling pathways reduced MG132-mediated upregulation of PAI-1 in varying degrees and most prominent effects were observed with SB203580, a p38 MAPK pathway inhibitor. The regulation of tPA/PAI-1 activity by proteasome inhibitor in rat primary astrocytes may underlie the observed CNS effects of MG132 such as neuroprotection.

• Applied Microscopy
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• 제40권4호
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• pp.211-218
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• 2010

포유동물의 난소는 호르몬과 감각신경 및 교감신경의 지배를 받아 난소 내 혈류의 조절, 스테로이드 호르몬 생성 및 난포의 발달과 관계된 난소의 고유기능이 조절되고 있다. 본 실험에서는 통상적인 추적자인 CT-HRP와 Pseudorabies바이러스(PRV)의 Bartha strain을 신경추적자로 이용하여 뇌하수체 후엽 및 난소와 연결된 중추신경부위를 밝히고자 하였다. 또 oxytocin을 난소 지배 신경축속에서 동정함으로써 신경축내 oxytocinergic neuron들의 존재를 확인하고, 이들이 배란을 중심으로 한 난소생식주기에 따라 보이는 중추 내 oxytocin신경세포의 변화를 조사하고자 하였다. Sprague-Dawley 흰쥐를 대상으로 난소 내에 PRV를 주사하고 48시간 후 실험동물들은 4% paraformaldehyde-lysine periodae로 고정하였으며, 뇌를 적출하여 $30{\mu}m$ 두께의 관상연속 절편을 만들어 CTHRP, PRV 및 oxytocin에 대한 삼중염색을 시행하였다. 본 실험 결과 후뇌에서부터 전뇌에 이르기까지 PRV에 양성반응을 보인 신경핵들이 관찰되어 난소를 지배하는 신경축을 구성할 수 있었다. 또 시상하부의 뇌실옆핵에서 oxytocin, PRV와 CT-HRP에 삼중으로 염색된 세포가 관찰됨으로써 신경내분비축과 자율신경축이 공동으로 기원하고 있다는 것을 형태학적으로 보여주었다. 따라서 oxytocin은 이 두 계통 내에서 호르몬의 역할과 신경전달물질의 역할을 겸할 것이라는 것을 추측할 수 있었다.

• Annals of Clinical Neurophysiology
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• 제5권2호
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• pp.181-186
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• 2003

Background: Somatosensory evoked potential (SSEP) is valuable for the evaluation of the central pathway. However, peripheral neuropathy sometimes renders the test useless by preventing the conduction from reaching the CNS. We postulated that the peripheral conduction problems could be overcome by proximal stimulation in SSEP and wanted to verify this in the study. Methods: Twenty patients with diabetic sensorimotor polyneuropathy were included. SSEP was elicited by stimulating the median and posterior tibial nerves. We compared the effect of distal and proximal stimulations in each SSEP in the aspect of presence/absence and various latencies of resultant waves. Results: Among the 40 cases, proximal stimulation caused reappearance of subsided waves in 10 cases (25%). In the median nerve SSEP, proximal stimulation made EN1 and CN2 visible which were not evident when distally stimulated. In the posterior tibial nerve SSEP, there was also improvement of forming waves when proximally stimulated. Conclusions: In the diabetic polyneuropathy, proximal stimulation of SSEP is more effective than the conventional distal stimulation in evaluating central pathway.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.277-289
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• 2018

The exponential increase in the use of mobile communication has triggered public concerns about the potential adverse effects of radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones on the central nervous system (CNS). In this study, we explored the relationship between calcium channels and apoptosis or autophagy in the hippocampus of C57BL/6 mice after RF-EMF exposure with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Firstly, the expression level of voltage-gated calcium channels (VGCCs), a key regulator of the entry of calcium ions into the cell, was confirmed by immunoblots. We investigated and confirmed that pan-calcium channel expression in hippocampal neurons were significantly decreased after exposure to RF-EMF. With the observed accumulation of autolysosomes in hippocampal neurons via TEM, the expressions of autophagy-related genes and proteins (e.g., LC3B-II) had significantly increased. However, down-regulation of the apoptotic pathway may contribute to the decrease in calcium channel expression, and thus lower levels of calcium in hippocampal neurons. These results suggested that exposure of RF-EMF could alter intracellular calcium homeostasis by decreasing calcium channel expression in the hippocampus; presumably by activating the autophagy pathway, while inhibiting apoptotic regulation as an adaptation process for 835 MHz RF-EMF exposure.

• 생약학회지
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• 제42권3호
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• pp.276-281
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• 2011

Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. The expression of HO-1 has cytoprotective effects in glutamate-induced oxidative cytotoxicity in HT22 cells. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various inducers is related to the nuclear transcription factor-E2-related factor 2 (Nrf2). Nrf2 is a master regulator of the antioxidant response. NNMBS008, the water-insoluble fraction of the 70% EtOH extract of roots of Sophora flavescens, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS008 makes the nuclear accumulation of Nrf2 pathway. In conclusion, the waterinsoluble fraction of the 70% EtOH extract of roots of S. flavescens (NNMBS008) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 pathway in mouse hippocampal HT22 cells. These results suggest that these extracts could be the effective candidates for the treatment of ROS-related neurological diseases.

• Journal of Oral Medicine and Pain
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• 제20권2호
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• pp.257-267
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• 1995

An Epidemiologic study was carried out on 77 TMD patients with degenerative joint disease who had visited the Orofacial Pain Clinic in Pusan National University Hospital. Al subjects were interviewed and examined clinically and radiologically using a standardized examination form. As related to gender and duration, subjective and objective sysmptoms in DJD patients were studied. The obtained results were as follows : 1. There were much more patients in the twenties or thirties, women and histories such as chronic duration and microtrauma. 2. Most patients responded positively more often to the questions of jaw function, unilateral chewing in habits, poot appetite and depression in behavioral response and shoulder pain in worsening prognosis 3. While the most common reasons for treatment were pain, noise, and limitation of opening, the associated symptoms such as headache, neckache, earache, jaw dysfunction, neck dysfunction, acute bite change and dizziness, ringing or fullness in the ears as secondary CNS excitatory effects were complained. 4. Opening the mouth in 25 to 40mm, soft end feel and deflective incisal pathway were seen and more tenderness to lateral or dorsal capsule of joint than intra or extra oral muscles were complained. 5. While there appeared no click, crepitus and single click in acute group, in chronic group, crepitus, single click and no click appeared in order of sequence. 6. Tomogram or bone scan revealed more bony changes than panorama and transcranial view.

• 생약학회지
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• 제41권3호
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• pp.190-195
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• 2010

Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as Parkinson's disease, Alzheimer's disease, epilepsy and ischemia. Inducible heme oxygenase (HO)-1 acts against oxidants that are thought to play a role in the pathogenesis of these diseases. NNMBS098, a composition comprising the water insoluble of the 70% EtOH extract of Zingiberis Rhizoma, showed the potent neuroprotective effects on glutamateinduced neurotoxicity by induced the expression of heme oxygenase (HO)-1 and increased HO activity in the mouse hippocampal HT22 cells. Furthermore, NNMBS098 caused the nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in mouse hippocampal HT22 cells. In addition, we found that treatment with c-Jun N-terminal kinase (JNK) inhibitor (SP600125) reduced NNMBS098-induced HO-1 expression and NNMBS098 also increased JNK phosphorylation. Therefore, these results suggest that NNMBS098 increases cellular resistance to glutamate-induced oxidative injury in mouse hippocampal HT22 cells, presumably through JNK pathway-Nrf2-dependent HO-1 expression.

• 대한청각학회지
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• 제24권1호
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• pp.48-52
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• 2020

Lateralization for central auditory processing (CAP) with dichotic digits recognition (DDR) test is believed expression of hemispheric dominance. Multiple sclerosis (MS) is considered an inflammatory and autoimmune alteration of central nervous system (CNS). Hearing alterations in MS and their role in CAP has not been well studied. A patient with MS and new kind of alteration in lateralization of CAP with DDR test is presented. A 53 year of age female with MS of 16 years of evolution, nine of them remained asymptomatic. She has a persistent advantage of the right ear for DDR test; but other monaural tests showed predominance of the left afferent pathway. Brainstem auditory evoked potentials (BAEPs) and long latency auditory evoked potentials (LLAEPs) showed adequate right response with deficits in organization of left response in BAEP, and N2 wave. In the contrary direction of previous publication, we disclosed advantage for DDR test, BAEP, and LLAEP in the right ear. We observed no left ear suppression; with predominance of correct left percentages in monaural psychoacoustics tests. We must keep on searching to find pathophysiological meaning of predominant of right or left auditory laterality as a CAP disorder in patients with MS.

• Journal of Audiology & Otology
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• 제24권1호
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• pp.48-52
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• 2020

Lateralization for central auditory processing (CAP) with dichotic digits recognition (DDR) test is believed expression of hemispheric dominance. Multiple sclerosis (MS) is considered an inflammatory and autoimmune alteration of central nervous system (CNS). Hearing alterations in MS and their role in CAP has not been well studied. A patient with MS and new kind of alteration in lateralization of CAP with DDR test is presented. A 53 year of age female with MS of 16 years of evolution, nine of them remained asymptomatic. She has a persistent advantage of the right ear for DDR test; but other monaural tests showed predominance of the left afferent pathway. Brainstem auditory evoked potentials (BAEPs) and long latency auditory evoked potentials (LLAEPs) showed adequate right response with deficits in organization of left response in BAEP, and N2 wave. In the contrary direction of previous publication, we disclosed advantage for DDR test, BAEP, and LLAEP in the right ear. We observed no left ear suppression; with predominance of correct left percentages in monaural psychoacoustics tests. We must keep on searching to find pathophysiological meaning of predominant of right or left auditory laterality as a CAP disorder in patients with MS.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.297-305
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• 1998

This study used in vivo intracellular recording in rat hippocampus to evaluate the effect of lidocaine and MK-801 on the membrane properties and the synaptic responses of individual neurons to electrical stimulation of the commissural pathway. Cells in control group typically fired in a tonic discharge mode with an average firing frequency of $2.4{\pm}0.9$ Hz. Neuron in MK-801 treated group (0.2 mg/kg, i.p.) had an average input resistance of $3.28{\pm}5.7\;M{\Omega}$ and a membrane time constant of $7.4{\pm}1.8$ ms. These neurons exhibited $2.4{\pm}0.2$ ms spike durations, which were similar to the average spike duration recorded in the neurons of the control group. Slightly less than half of these neurons were firing spontaneously with an average discharge rate of $2.4{\pm}1.1$ Hz. The average peak amplitude of the AHP following the spikes in these groups was $7.4{\pm}0.6$ mV with respect to the resting membrane potential. Cells in MK-801 and lidocaine treated group (5 mg/kg, i.c.v.) had an average input resistance of $3.45{\pm}6.0\;M{\Omega}$ and an average time constant of $8.0{\pm}1.4$ ms. The cells were firing spontaneously at an average discharge rate of $0.6{\pm}0.4$ Hz. Upon depolarization of the membrane by 0.8 nA for 400 ms, all of the tested cells exhibited accommodation of spike discharge. The most common synaptic response contained an EPSP followed by early-IPSP and late-IPSP. Analysis of the voltage dependence revealed that the early-IPSP and late-IPSP were putative $Cl^--and\;K^+-dependent$, respectively. Systemic injection of the NMDA receptor blocker, MK-801, did not block synaptic responses to the stimulation of the commissural pathway. No significant modifications of EPSP, early-IPSP, or late-IPSP components were detected in the MK-801 and/or lidocaine treated group. These results suggest that MK-801 and lidocaine manifest their CNS effects through firing pattern of hippocampal pyramidal cells and neural network pattern by changing the synaptic efficacy and cellular membrane properties.