• 한국약용작물학회지
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• 제16권6호
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• pp.409-415
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• 2008

Moutan cortex, the root bark of Paeonia suffruticosa Andrews (Paeoniaceae), has pharmacological effects such as anti-inflammatory, antiallergic, analgesic and antioxidant activities. We investigated a methanol extract of Moutan cortex for neuroprotective effects on neurotoxicity induced by amyloid ${\beta}$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons. Exposure of cultured cortical neurons to $10\;{\mu}M\;A{\beta}$ (25-35) for 24 h induced neuronal apoptotic death. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced neuronal cell death at 30 and $50\;{\mu}g/m{\ell}$, which was measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. Moutan cortex inhibited $10\;{\mu}M\;A{\beta}$ (25-35)-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) which were measured by fluorescent dyes. Moutan cortex also inhibited glutamate release into medium induced by $10\;{\mu}M\;A{\beta}$ (25-35), which was measured by HPLC. These results suggest that Moutan cortex prevents $A{\beta}$ (25-35)-induced neuronal cell damage by interfering with the increase of $[Ca^{2+}]_i$, and then inhibiting glutamate release and ROS generation. Moutan cortex may have a therapeutic role in preventing the progression of Alzheimer's disease.

• The Journal of Korean Physical Therapy
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• 제23권6호
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• pp.49-53
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• 2011

Purpose: The purpose of this study is to investigate whether dual-hemisphere transcranial direct current stimulation (tDCS) could induce more cortical activity, compared to single-hemisphere, using functional MRI (fMRI). Methods: One right-handed healthy subject was recruited. Three phases of dual-hemisphere tDCS (i.e. anodal tDCS over the left-dominant primary sensoriomotor cortex (SM1) and cathodal tDCS over the right-non dominant SM(1) were consecutively delivered on to a subject, during fMRI scanning. The voxel count and the intensity index in the averaged cortical map were analyzed among the three tDCS phases. Results: Our result showed that cortical activation was observed on all the three phases of the dual-hemisphere tDCS. Voxel count and intensity index were as following; 912 and 4.07 in the first phase, 1102 and 3.90 in the second phase, 1031 and 3.80 in the third phase. Conclusion: This study demonstrated that application of the dual-hemisphere tDCS could induce cortical activity and maintain to recruit cortical neurons. Our findings suggested that application of dual-hemisphere tDCS could produce efficiency of the ongoing tDCS effect to facilitate cortical excitability.

• BMB Reports
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• 제49권2호
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• pp.71-72
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• 2016

Focal cortical dysplasia type II (FCDII) is a focal malformation of the developing cerebral cortex and the major cause of intractable epilepsy. However, since the molecular genetic etiology of FCD has remained enigmatic, the effective therapeutic target for this condition has remained poorly understood. Our recent study on FCD utilizing various deep sequencing platforms identified somatic mutations in MTOR (existing as low as 1% allelic frequency) only in the affected brain tissues. We observed that these mutations induced hyperactivation of the mTOR kinase. In addition, focal cortical expression of mutant MTOR using in utero electroporation in mice, recapitulated the neuropathological features of FCDII, such as migration defect, cytomegalic neuron and spontaneous seizures. Furthermore, seizures and dysmorphic neurons were rescued by the administration of mTOR inhibitor, rapamycin. This study provides the first evidence that brain somatic activating mutations in MTOR cause FCD, and suggests the potential drug target for intractable epilepsy in FCD patients.

• BMB Reports
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• 제51권1호
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• pp.3-4
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• 2018

Parkinson's disease (PD) is a debilitating disorder resulting from loss of dopamine neurons. In dopamine deficient state, the basal ganglia increases inhibitory synaptic outputs to the thalamus. This increased inhibition by the basal ganglia output is known to reduce firing rate of thalamic neurons that relay motor signals to the motor cortex. This 'rate model' suggests that the reduced excitability of thalamic neurons is the key for inducing motor abnormalities in PD patients. We reveal that in response to inhibition, thalamic neurons generate rebound firing at the end of inhibition. This rebound firing increases motor cortical activity and induces muscular responses that triggers Parkinsonian motor dysfunction. Genetic and optogenetic intervention of the rebound firing prevent motor dysfunction in a mouse model of PD. Our results suggest that inhibitory synaptic mechanism mediates motor dysfunction by generating rebound excitability in the thalamocortical pathway.

• Applied Microscopy
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• 제41권4호
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• pp.249-255
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• 2011

신경세포는 생존 및 정상적인 기능을 위하여 다량의 에너지를 소비하므로, 미토콘드리아의 기능이 매우 중요하다. 미토콘드리아는 신경세포 내에서 신경돌기를 따라 이동하기도 하고, 세포내 여러 상황에 따라 접합과 절단을 반복하면서 그 분포와 형태가 역동적으로 변화한다. 역동적인 미토콘드리아의 형태 변화는 주로 GTPase 단백질인 Dynamin-related protein-1 (Drp1)에 의한 절단에 의해 조절되는 것으로 알려져 있다. 그러나, 중추신경계 신경세포에서의 미토콘드리아 분포 및 형태 변화 조절에 대해서는 비교적 연구가 미흡한 실정이다. 이 연구의 저자들은 미토콘드리아에 선택적으로 표적화되는 DsRed-mito 플라스미드를 일차 배양한 대뇌겉질 신경세포에 유전자 도입하여, 가지돌기 및 축삭에 분포하는 미토콘드리아의 길이와 역동성을 분석하였다. 흥미롭게도, 축삭 말단 부위에 분포하는 미토콘드리아의 길이가 세포체 근처의 축삭에 분포하는 미토콘드리아에 비하여 유의미하게 짧았다. 또한 Drp1 단백질이 가지돌기와 축삭에 다량 분포하며, 형광현미경하에서 이뤄진 실시간 촬영을 통해 축삭내에서 미토콘드리아의 절단이 활발하게 나타나는 것을 관찰하였다. 이를 통해, 축삭 말단 미토콘드리아의 길이 감소는 축삭 내 분포하는 Drp1 단백질의 활성에 의한 것으로 생각할 수 있었다. 위 가설을 검증하기 위하여, Drp1의 우성음성돌연변이 단백질을 신경세포에 유전자 도입하여 내재적 Drp1의 활성을 억제한 결과, 축삭 내 미토콘드리아 길이의 유의미한 증가가 관찰되었다. 이러한 결과들을 종합할 때, 대뇌겉질 신경세포에서 미토콘드리아의 절단은 축삭 내에서 지엽적으로도 진행되며, 이에 의하여 축삭내 위치에 따른 미토콘드리아의 길이 변화가 조절되는 것으로 생각되었다.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.311-319
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• 2018

Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (${\Delta}{\psi}_m$). Therefore, pharmacological manipulation of ${\Delta}{\psi}_m$ can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ${\Delta}{\psi}_m$ against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity ($100{\mu}M$, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate ($100{\mu}M$)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of $Ca^{2+}$ ($5{\mu}M$). Nobiletin-induced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ${\Delta}{\psi}_m$ were completely abolished in $K^+-free$ medium on pure isolated mitochondria. Taken together, results demonstrate that $K^+$ influx into mitochondria is critically involved in partial mitochondrial depolarization-related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial $K^+$ influx is probably mediated, at least in part, by activation of mitochondrial $K^+$ channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

• Journal of Ginseng Research
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• 제42권3호
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• pp.298-303
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• 2018

Background: Panax ginseng is one of the most commonly used medicinal herbs worldwide for a variety of therapeutic properties including neurocognitive effects. Ginsenoside Rg1 is one of the most abundant active chemical constituents of this herb with known neuroprotective, anxiolytic, and cognition improving effects. Methods: We investigated the effects of Rg1 on the medial prefrontal cortex (mPFC), a key brain region involved in cognition, information processing, working memory, and decision making. In this study, the effects of systemic administration of Rg1 (1 mg/kg, 3 mg/kg, or 10 mg/kg) on (1) spontaneous firing of the medial prefrontal cortical neurons and (2) long-term potentiation (LTP) in the hippocampal-medial prefrontal cortical (HP-mPFC) pathway were investigated in male Sprague-Dawley rats. Results: The spontaneous neuronal activity of approximately 50% the recorded pyramidal cells in the mPFC was suppressed by Rg1. In addition, Rg1 attenuated LTP in the HP-mPFC pathway. These effects were not dose-dependent. Conclusion: This report suggests that acute treatment of Rg1 impairs LTP in the HP-mPFC pathway, perhaps by suppressing the firing of a subset of mPFC neurons that may contribute to the neurocognitive effects of Rg1.

• Molecules and Cells
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• 제39권6호
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• pp.501-507
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• 2016

The corpus callosum is a bundle of nerve fibers that connects the two cerebral hemispheres and is essential for coordinated transmission of information between them. Disruption of early stages of callosal development can cause agenesis of the corpus callosum (AgCC), including both complete and partial callosal absence, causing mild to severe cognitive impairment. Despite extensive studies, the etiology of AgCC remains to be clarified due to the complicated mechanism involved in generating AgCC. The biological function of PI3K signaling including phosphatidylinositol-3,4,5-trisphosphate is well established in diverse biochemical processes including axon and dendrite morphogenesis, but the function of the closely related phosphatidylinositol-3,4,-bisphosphate (PI(3,4)P2) signaling, particularly in the nervous system, is largely unknown. Here, we provide the first report on the role of inositol polyphosphate 4-phosphatase II (INPP4B), a PI(3,4)P2 metabolizing 4-phosphatase in the regulation of callosal axon formation. Depleting INPP4B by in utero electroporation suppressed medially directed callosal axon formation. Moreover, depletion of INPP4B significantly attenuated formation of Satb2-positive pyramidal neurons and axon polarization in cortical neurons during cortical development. Taken together, these data suggest that INPP4B plays a role in the regulating callosal axon formation by controlling axon polarization and the Satb2-positive pyramidal neuron population. Dysregulation of INPP4B during cortical development may be implicated in the generation of partial AgCC.

• 사상체질의학회지
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• 제11권2호
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• pp.267-281
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• 1999

1. 연구목적 본 실험은 태음조위탕이 대뇌신경세포의 산화적 손상에 대한 효능을 밝히기 위한 것이다. 2. 연구방법 신생생쥐에서 순수 분리한 대뇌신경세포(大腦神經細胞)를 배양(培養)하여 glucose oxidase (GO)에 노출시킨 후 이의 독성효과(毒性效果)를 측정(測定)하였으며, 또한 GO에 의하여 유도(誘導)된 독성(毒性)에 대한 태음조위탕(太陰調胃湯)의 효과(效果)를 조사(調査)하였다. 3. 결과 및 결론 산소자유기(酸素自由基)인 GO는 MTTassay에 의한 세포생존율(細胞生存率)의 유의한 감소(減少)를 보였다. 산소자유기(酸素自由基)인 GO는 NR assay에 의한 세포생존율(細胞生存率)의 유의한 감소(減少)를 보였다. GO의 산화적(酸化的) 손상(損傷)에 의한 신경독성(神經毒性)에 대하여 태음조위탕(太陰調胃湯) 투여로 총단백질양의 유의한 증가(增加)를 보였다. GO의 산화적(酸化的) 손상(損傷)에 의한 신경독성(神經毒性)에 대하여 태음조위탕(太陰調胃湯) 투여로 lipid peroxidation의 유의한 감소(減少)를 보였다. 이상(以上)의 실험결과(實驗結果)는 태음조위탕(太陰調胃湯)이 대뇌신경세포(大腦神經細胞)의 산화적손상(酸化的損傷)에 대하여 유의성(有意性) 있는 방어적(防禦的) 작용(作用)을 나타낸 것으로, 이와 관련된 노화억제(老化抑制)나 뇌허혈(腦虛血), 다발성경화증(多發性硬化症), 치매 등 뇌기능손상(腦機能損傷)이나 저하(低下)로 유발되는 질환(疾患)에 대한 임상응용(臨床應用)에 대해서도 지속적(持續的)인 연구(硏究)가 필요(必要)하다고 사료(思料)된다.

• 수면정신생리
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• 제2권2호
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• pp.133-137
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• 1995

The author reviews current knowledge about what REM sleep is and where and how it is generated. REM sleep is the state in which our most vivid dreams occur. REM sleep is identified by the simultaneous presence of a desynchronized cortical EEG, an absence of activity in the antigravity muscles(atonia), and periodic bursts of rapid eye movements. Another characteristic phenomena of REM sleep are the highly synchronized hippocampal EEG of theta frequency and the ponto-geniculo-occipital(PGO) spike. All these phenomena can be explained in terms of changes in neuronal activity. Transection studies have determined that the pons is sufficient for generating REM sleep. Lesion studies have identified a small region in the lateral pontine tegmentum corresponding to lateral portions of the nucleus reticularis pontis oralis(RPO) and the region immediately ventral to the locus coeruleus, which is required for REM sleep. Unit recording studies have found a population of cells within this region that is selectively active in REM sleep. Cholinergic neurons of the giant cell field of pontine tegmentum(ETG), which is 'REM a sleep-on cells', has shown to be critically involved in the generation of REM sleep. Noradrenergic neurons of the locus coeruleus and serotonergic neurons of the dorsal raphe, which are called 'REM sleep-off cells', appear to act in a reciprocal manner to the cholinergic neurons. It is proposed that the periodic cessations of discharge of 'REM sleep-off cells' during REM sleep might be significant for the prevention of the desensitization of receptors of these neurons.