• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.71-80
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• 2002

Previous studies have suggested that brain stem noradrenergic inputs differentially modulate neurons in the paraventricular nucleus (PVN). Here, we compared the effects of norepinephrine (NE) on spontaneous GABAergic inhibitory postsynaptic currents (sIPSCs) in identified PVN neurons using slice patch technique. In 17 of 18 type I neurons, NE $(30{\sim}100{\mu}M)$ reversibly decreased sIPSC frequency to $41{\pm}7%$ of the baseline value $(4.4{\pm}0.8\;Hz,\;p<0.001).$ This effect was blocked by yohimbine $(2{\sim}20{\mu}M),$ an ${\alpha}_2-adrenoceptor$ antagonist and mimicked by clonidine $(50{\mu}M),$ an ${\alpha}_2-adrenoceptor$ agonist. In contrast, NE increased sIPSC frequency to $248{\pm}32%$ of the control $(3.06{\pm}0.37\;Hz,\;p<0.001)$ in 31 of 54 type II neurons, but decreased the frequency to $41{\pm}7$ of the control $(5.5{\pm}1.3\;Hz)$ in the rest of type II neurons (p<0.001). In both types of PVN neurons, NE did not affect the mean amplitude and decay time constant of sIPSCs. In addition, membrane input resistance and amplitude of sIPSC of type I neurons were larger than those of type II neurons tested (1209 vs. 736 $M{\Omega},$ p<0.001; 110 vs. 81 pS, p<0.001). The results suggest that noradrenergic modulation of inhibitory synaptic transmission in the PVN decreases the neuronal excitability in most type I neurons via ${\alpha}_2-adrenoceptor,$ however, either increases in about 60% or decreases in 40% of type II neurons.

• 전자공학회논문지S
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• 제36S권8호
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• pp.39-47
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• 1999

본 논문에서는 포항제철의 열연 권취 온도 공정을 제어하기 위한 방법으로 온라인 재학습 가능한 RBF 네트워크(Radial Basis Function network)를 제안한다. 새로 제안된 신경회로망 모델을 이용해 권취 온도 제어 시스템의 열전달 계수를 생성해주는 기조의 규칙 기반 계수표를 대체할 수 있다. 열연 공정 작업의 시간에 따른 변화를 고려하도록 지존의 RBF 네트워크에 부가적인 온라인 재학습용 시냅스 가중치를 도입한다. 부가적인 가중치들로 인해 이미 학습된 전체 데이터들의 특성 정보를 유지하면서 새로 들어오는 데이터들에 대해 온라인 재학습이 이루어진다. 따라서, 제안된 RBF 네트워크는 파국적 간섭(catastrophic interference)효과를 상당히 감소시킬 수 있다. 그리고 거부 네트워크을 도입하여 제어기의 신뢰도을 높일 수 있었고, 실제 현장에 적용한 실험 결과는 기존의 방법보다 평균 2.2퍼센트이상 향상된 성능을 보였다.

• BMB Reports
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• 제53권4호
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• pp.234-239
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• 2020

Epilepsy is a chronic neurological disease characterized by spontaneous recurrent seizures and caused by various factors and mechanisms. Malfunction of the olfactory bulb is frequently observed in patients with epilepsy. However, the morphological changes in the olfactory bulb during epilepsy-induced neuropathology have not been elucidated. Therefore, in the present study, we investigated the expression of parvalbumin (PV), one of the calcium-binding proteins, and morphological changes in the rat main olfactory bulb (MOB) following pilo-carpine-induced status epilepticus (SE). Pilocarpine-induced SE resulted in neuronal degeneration in the external plexiform layer (EPL) and glomerular layer (GL) of the MOB. PV immunoreactivity was observed in the neuronal somas and processes in the EPL and GL of the control group. However, six hours after pilocarpine administration, PV expression was remarkably decreased in the neuronal processes compared to the somas and the average number of PV-positive interneurons was significantly decreased. Three months after pilocarpine treatment, the number of PV-positive interneurons was also significantly decreased compared to the 6 hour group in both layers. In addition, the number of NeuN-positive neurons was also significantly decreased in the EPL and GL following pilocarpine treatment. In double immunofluorescence staining for PV and MAP2, the immunoreactivity for MAP2 around the PV-positive neurons was significantly decreased three months after pilocarpine treatment. Therefore, the present findings suggest that decreases in PV-positive GABAergic interneurons and dendritic density in the MOB induced impaired calcium buffering and reciprocal synaptic transmission. Thus, these alterations may be considered key factors aggravating olfactory function in patients with epilepsy.

• 생약학회지
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• 제42권2호
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• pp.175-181
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• 2011

Oxidative stress or 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 is one of the major excitatory neurotransmitter in the central nervous system (CNS). Glutamate contributes to fast synaptic transmission, neuronal plasticity, outgrowth and survival, behavior, learning and memory. In spite of these physiological functions, high concentration of glutamate causes neuronal cell damage, acute insults and chronic neuronal neurodegenerative diseases. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. NNMBS020, the water-insoluble fraction of the 70% EtOH extract of root barks of Dictamnus dasycarpus, 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, NNMBS020 makes the nuclear accumulation of Nrf2 and stimulates extracellular signal-regulated kinase (ERK) pathway. The ERK MAPK pathway inhibitor significantly reduced NNMBS020-induced HO-1 expression, whereas the JNK and p38 inhibitors did not. In conclusion, the water-insoluble fraction of the 70% EtOH extract of root barks of D. dasycarpus (NNMBS020) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 and ERK pathway in mouse hippocampal HT22 cells.

• 동의생리병리학회지
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• 제21권2호
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• pp.432-437
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• 2007

Reactive oxygen species (ROS) are toxic agents that may be involved in various neurodegenerative diseases. Recent studies indicate that ROS are also involved in persistent pain through a spinal mechanism. In the present study, whole cell patch clamp recordings were carried out on substantia gelatinosa (SG) neurons in spinal cord slice of neonatal rats to investigate the effects of ROS on neuronal excitability and excitatory synaptic transmission. In current clamp condition, tert-buthyl hydroperoxide (t-BuOOH), an ROS donor, induced a electrical hyperexcitability during t-BuOOH wash-out followed by a brief inhibition of excitability in SG neurons. Application of t-BuOOH depolarized membrane potential of SG neurons and increased the neuronal firing frequencies evoked by depolarizing current pulses. Phenyl-N-tert-buthylnitrone (PBN), an ROS scavenger, antagonized t-BuOOH induced hyperexcitability. IN voltage clamp conditions, t-BuOOH increased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). In order to determine the site of action of t-BuOOH, miniature excitatory postsynaptic currents (mEPSCs) were recorded. t-BuOOH increased the frequency and amplitude of mEPSCs, indicating that it may modulate the excitability of the SG neurons via pre- and postsynaptic actions. These data suggest that ROS generated by peripheral nerve injury can induce central sensitization in spinal cord.

• Biomolecules & Therapeutics
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• 제20권1호
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• pp.1-18
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• 2012

Schizophrenia is a devastating psychiatric illness that afflicts 1% of the population worldwide, resulting in substantial impact to patients, their families, and health care delivery systems. For many years, schizophrenia has been felt to be associated with dysregulated dopaminergic neurotransmission as a key feature of the pathophysiology of the illness. Although numerous studies point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot completely account for all of the symptoms seen in schizophrenia, and dopamine-based treatments are often inadequate and can be associated with serious side effects. More recently, converging lines of evidence have suggested that there are abnormalities of glutamate transmission in schizophrenia. Glutamatergic neurotransmission involves numerous molecules that facilitate glutamate release, receptor activation, glutamate reuptake, and other synaptic activities. Evidence for glutamatergic abnormalities in schizophrenia primarily has implicated the NMDA and AMPA subtypes of the glutamate receptor. The expression of these receptors and other molecules associated with glutamate neurotransmission has been systematically studied in the brain in schizophrenia. These studies have generally revealed region- and molecule-specifi c changes in glutamate receptor transcript and protein expression in this illness. Given that glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia, recent drug development efforts have targeted the glutamate system. Much effort to date has focused on modulation of the NMDA receptor, although more recently other glutamate receptors and transporters have been the targets of drug development. These efforts have been promising thus far, and ongoing efforts to develop additional drugs that modulate glutamatergic neurotransmission are underway that may hold the potential for novel classes of more effective treatments for this serious psychiatric illness.

• 한국재료학회지
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• 제27권1호
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• pp.32-38
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• 2017

Insulating $TaN_x$ films were grown by plasma enhanced atomic layer deposition using butylimido tris dimethylamido tantalum and $N_2+H_2$ mixed gas as metalorganic source and reactance gas, respectively. Crossbar devices having a $Pt/TaN_x/Pt$ stack were fabricated and their electrical properties were examined. The crossbar devices exhibited temperature-dependent nonlinear I (current) - V (voltage) characteristics in the temperature range of 90-300 K. Various electrical conduction mechanisms were adopted to understand the governing electrical conduction mechanism in the device. Among them, the PooleFrenkel emission model, which uses a bulk-limited conduction mechanism, may successfully fit with the I - V characteristics of the devices with 5- and 18-nm-thick $TaN_x$ films. Values of ~0.4 eV of trap energy and ~20 of dielectric constant were extracted from the fitting. These results can be well explained by the amorphous micro-structure and point defects, such as oxygen substitution ($O_N$) and interstitial nitrogen ($N_i$) in the $TaN_x$ films, which were revealed by transmission electron microscopy and UV-Visible spectroscopy. The nonlinear conduction characteristics of $TaN_x$ film can make this film useful as a selector device for a crossbar array of a resistive switching random access memory or a synaptic device.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.163-169
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• 2011

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by $x^2$-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

• Archives of Pharmacal Research
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• 제23권5호
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• pp.525-530
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• 2000

mST3GaIV synthesizes ganglioside GM3, the precursor for simple and complex a- and b- series gangliosides, and the expression and regulation of mST3GaIV (CMP-NeuAc: lactosylceramide $\alpha$2,3-sialyltransferase) activity is central to the production of almost all gangliosides, a class of glycosphingolipids implicated in variety of cellular processes such as transmembrane signaling, synaptic transmission, specialized membrane domain formation and cell-cell interactions. To understand the developmental expression of mST3GaIV in mice, we investigated the spatial and temporal expression of mST3GaIV mRNA during the mouse embryogenesis [embryonic (E) days; 19, E11, E13, E15] by in situ hybridization with digoxigenin-labeled RNA probes. All tissues from 19 and E11 were positive for mST3GaIV mRNA. On E13, mST3GaIV mRNA was expressed in various neural and non-neural tissues. In contrast to these, on E15, the telencephalon and liver produced a strong expression of mST3GaIV which was a quite similar to that of E13. In this stage, mST3GaIV mRNA was also expressed in some non-neural tissues. These data indicate that mST3GaIV is differently expressed at developmental stages of embryo, and this may be importantly related with regulation of organogenesis in mice.

• 대한수의학회지
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• 제11권1호
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• pp.59-63
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• 1971

Current interest in ${\gamma}$-aminobutyric acid (GABA) has arisen from the convergence of several independent line of investigation leading to the demonstration that this and related substances are normal products of brain metabolism and that GABA has an important physiological action upon brain function as well as upon certain peripheral nervous structures. The interest for neurophysiologists has been enhanced by the importance of the discovery for the role of humoral mediator of synaptic transmission or regulator of neuronal activity in the central nervous system, particularly if it may shed some elight upon the nature of central inhibitory processes. In accordance with such an interest and importance, this work was performed in order to standardize the normal content as a preliminary investigation of so-called night active and daytime active animals GABA content in their brains when they are exposed to light and darkness. The method, through which the estimation has made in this work, was paper chromatographic method developed by Maynert and Klingman for the estimation of GABA content in animal tissues. The results obtained are summerized as follows: 1) GABA content in the cerebral cortex of house rat ranged from 90 to $310{\mu}g/gm$ of wet weight. 2) The content of GAGA ranging from 130 to $510{\mu}g/gm$ of wet weight was occurred from midbrain of the rat. 3) GABA content was ranged from 30 to $150 {\mu}g/gm$ of wet weight of the rat cerebellum. 4) The contents of fowl cerebral cortex, midbrain, and cerebellum are estimated as ranging 230-590, 250-620, $50-280{\mu}g/gm$ of wet weight, respectively. As a result, it may be concluded that among three brain tissues of both animals the midbrain is the highest region in GABA content. Fowl brain, on the other side, contains more higher GABA content than the house rat brain does.