• Journal of Ginseng Research
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• 제34권3호
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• pp.246-253
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• 2010

Ginsenoside $Rg_3$ ($Rg_3$), one of the active ingredients in Panax ginseng, attenuates NMDA receptor-mediated currents in vitro and antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. In the present study, we examined the neuroprotective effects of $Rg_3$ on 24-hydroxycholesterol (24-OH-chol)-induced cytotoxicity in vitro. The results showed that $Rg_3$ treatment significantly and dose-dependently inhibited 24-OH-chol-induced cell death in rat cultured cortical neurons, with an $IC_{50}$ value of $28.7{\pm}7.5\;{\mu}m$. Furthermore, the $Rg_3$ treatment not only significantly reduced DNA damage, but also dose-dependently attenuated 24-OH-chol-induced caspase-3 activity. To study the mechanisms underlying the in vitro neuroprotective effects of $Rg_3$ against 25-OH-chol-induced cytotoxicity, we also examined the effect of $Rg_3$ on intracellular $Ca^{2+}$ elevations in cultured neurons and found that $Rg_3$ treatment dose-dependently inhibited increases in intracellular $Ca^{2+}$, with an $IC_{50}$ value of $40.37{\pm}12.88\;{\mu}m$. Additionally, $Rg_3$ treatment dose-dependently inhibited apoptosis with an $IC_{50}$ of $47.3{\pm}14.2\;{\mu}m$. Finally, after confirming the protective effect of $Rg_3$ using a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, we found that $Rg_3$ is an active component in ginseng-mediated neuroprotection. These results collectively indicate that $Rg_3$-induced neuroprotection against 24-OH-chol in rat cortical neurons might be achieved via inhibition of a 24-OH-chol-mediated $Ca^{2+}$ channel. This is the first report to employ cortical neurons to study the neuroprotective effects of $Rg_3$ against 24-OH-chol. In conclusion, $Rg_3$ was effective for protecting cells against 24-OH-chol-induced cytotoxicity in rat cortical neurons. This protective ability makes $Rg_3$ a promising agent in pathologies implicating neurodegeneration such as apoptosis or neuronal cell death.

• Natural Product Sciences
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• 제18권1호
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• pp.26-31
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• 2012

Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to $500{\mu}M$ glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited $500{\mu}M$ glutamate-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and $H_2DCF$-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting $[Ca^{2+}]_i$ elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.12-20
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• 1998

Primary neuronal culture was studied for observing effect of ginsenoside Rgl (Rgl) on serum-free medium induced apoptosis. Results showed that Rgl at concentration of 1 umol$.$ L-1 and 10 umol$.$L-1 could inhibit apoptosis, decrease intracellular calcium concentration in cultured cortical neurons, enhance SOD activity in both aged rat cortex and cultured cortical neurons, scavenge cytotoxic oxygen free radicals, decrease NO content and NOS activity in aged rat cortex and cultured cortical neurons, increase bel-2 gene expression in rat brain. These results provided new data for elucidating the anti-aging effect of Rgi. Rgl is considered to be a useful drug for treatment of Alzheimer's disease and brain aging.

• Journal of Korean Neurosurgical Society
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• 제46권1호
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• pp.1-4
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• 2009

Objective: To report an unsuspected adaptive plasticity of single upper motor neurons and of primary motor cortex found after microsurgical connection of the spinal cord with peripheral nerve via grafts in paraplegics and focussed discussion of the reviewed literature. Methods: The research aimed at making paraplegics walk again, after 20 years of experimental surgery in animals. Amongst other things, animal experiments demonstrated the alteration of the motor endplates receptors from cholinergic to glutamatergic induced by connection with upper motor neurons. The same paradigm was successfully performed in paraplegic humans. The nerve grafts were put into the ventral-lateral spinal tract randomly, with out possibility of choosing the axons coming from different areas of the motor cortex. Results: The patient became able to selectively activate the re-innervated muscles she wanted without concurrent activities of other muscles connected with the same cortical areas. Conclusion: Authors believe that unlike in nerve or tendon transfers, where the whole cortical area corresponding to the transfer changes its function a phenomenon that we call "brain plasticity by areas". in our paradigm due to the direct connection of upper motor neurons with different peripheral nerves and muscles via nerve grafts motor learning occurs based on adaptive neuronal plasticity so that simultaneous contractions of other muscles are prevented. We propose to call it adaptive functional "plasticity by single neurons". We speculate that this phenomenon is due to the simultaneous activation of neurons spread in different cortical areas for a given specific movement, whilst the other neurons of the same areas connected with peripheral nerves of different muscles are not activated at the same time. Why different neurons of the same area fire at different times according to different voluntary demands remains to be discovered. We are committed to solve this enigma hereafter.

• 한국약용작물학회지
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• 제15권2호
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• pp.105-111
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• 2007

The protective effect of ethanol extract of Korean mistletoe (KM; Viscum album coloratum) on hydrogen peroxide $(H_{2}O_{2})-induced$ neurotoxicity was examined in primary cultured rat cortical neurons. $H_{2}O_{2}$ reduced viability of cortical neurons in a concentration-dependent manner. The addition of KM, over a concentration range of 10 to 100 ${\mu}g/ml$, concentration-dependently prevented the $H_{2}O_{2}(100\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-di-phenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. KM significantly inhibited $H_{2}O_{2}-induced$ elevation of the cytosolic $Ca^{2+}$ concentration $([Ca^{2+}]_{c})$, which was measured by a fluorescent dye, fluo-4 AM. KM inhibited glutamate release into medium and generation of reactive oxygen species (ROS) induced by $H_{2}O_{2}$. These results suggest that KM may mitigate the $H_{2}O_{2}-induced$ neurotoxiciy by interfering with the increase of $[Ca^{2+}]_{c}$, and inhibiting glutamate release and generation of ROS in cultured neurons.

• The Korean Journal of Physiology
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• 제27권1호
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• pp.79-91
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• 1993

The present study was carried out to determine the effects of cocaine (0.25, 1.0, 10.0 mg/kg, i.p.) on the interactions between spontaneously active neurons within ensembles of simultaneously recorded neurons in the primary somatosensory cortex (Sl, n= 20) and the ventroposterolateral (VPL, n= 16) thalamic nucleus of awake rats. Spike triggered cross correlation histograms were constructed between pairs of simultaneously recorded neurons. Among 101 neuronal pairs analyzed, 22.7% showed correlations indicative of various functional connections among the cortical cells, two corticothalamic interactions and one thalamocortical excitatory interaction. There were also 15 cofiring activities among SI cortical cells. These functional connectivities appeared to be modulated (weakened, abolished, or strengthened) during the 5 to 30 min following cocaine injection. The effects of saline were tested as a control, but it did not appear to alter the functional connectivities. In general, cocaine-induced changes of the functional interactions were mainly due to the concomitant alterations of the uncorrelated background discharges. These results suggest that the biphasic effects of cocaine on the spontaneously established neural networks among the SI cortical and the VPL thalamic cells of conscious rat were mainly indirect. However, various changes of the functional interactions by different doses of cocaine appeared to be a possible neural network mechanism for the cocaine induced modulation of afferent somatosensory transmission.

• Molecules and Cells
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• 제24권3호
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• pp.416-423
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• 2007

Alterations in the glycan chains of cell surface glycoconjugates are frequently involved biological processes such as cell-cell interaction, cell migration, differentiation and development. Cultured embryonic (E18) rat cortical neurons underwent apoptosis in response to camptothecin, and lectin histochemistry showed that binding to apoptotic neurons of FITC-conjugated Maackia amurensis agglutinin (MAA), which is specific for terminal ${\alpha}2,3$-sialic acid residues, increased progressively with increasing concentrations of camptothecin. Analysis of the total proteins of apoptotic neurons by SDS-PAGE, and lectin blotting using HRP-labeled MAA, revealed that the expression of terminal ${\alpha}2,3$-sialic acid residues on an unknown protein with an apparent molecular mass of 25.6 kDa also increased in apoptotic neurons. NP-HPLC analysis of the total cellular N-glycans of normal and apoptotic neurons demonstrated that the expression of structurally simpler biantennary types of N-glycans fell by 49% during apoptosis whereas the more branched triantennary types of N-glycans with terminal sialic acid residues increased by up to 59%. These results suggest that increased surface expression of ${\alpha}2,3$-sialic acid residues and hyperglycosylation of N-glycans is a common feature of cellular responses to changes in cell physiology such as tumorigenesis and apoptosis.

• 한국약용작물학회지
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• 제19권1호
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• pp.31-37
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• 2011

Previous work demonstrated that an ethanol extract (HS0608) of a mixture of three medicinal plants of Curcuma longae radix, Phellinus linteus, and Scutellariae radix markedly inhibits $A{\beta}$ (25-35)-induced neurotoxicity. The present study was performed to further verify the neuroprotective effect of HS0608 on oxidative and ischemic cerebral injury using cultured rat cortical neurons and rats. Exposure of cultured cortical neurons to $100\;{\mu}M$ hydrogen peroxide ($H_2O_2$) induced neuronal apoptotic death. At $10-100{\mu}g/ml$, HS0608 inhibited neuronal death, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) induced by $H_2O_2$ in primary cultures of rat cortical neurons. In vivo, HS0608 prevented cerebral ischemic injury induced by 2-h middle cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct and edema were significantly reduced in rats that received HS0608 (200 mg/kg). These results suggest that the anti-oxidative properties of HS0608 may be responsible for its neuroprotective effect against focal cerebral ischemic injury and that HS0608 may have a therapeutic role in neurodegenerative diseases such as stroke.

• BMB Reports
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• 제48권2호
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• pp.97-102
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• 2015

Neurons in the developing brain form the cortical plate (CP) in an inside-out manner, in which the late-born neurons are located more superficially than the early-born neurons. Fyn, a member of the Src family kinases, plays an important role in neuronal migration by binding to many substrates. However, the role of the Src-homology 2 (SH2) domain in function of Fyn in neuronal migration remains poorly understood. Here, we demonstrate that the SH2 domain is essential for the action of Fyn in neuronal migration and cortical lamination. A point mutation in the Fyn SH2 domain ($Fyn^{R176A}$) impaired neuronal migration and their final location in the cerebral cortex, by inducing neuronal aggregation and branching. Thus, we provide the first evidence of the Fyn SH2 domain contributing to neuronal migration and neuronal morphogenesis.

• 대한약리학회지
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• 제32권2호
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• pp.169-175
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• 1996

The reactivity of the sulfhydryl (thiol) group of homocysteine has been associated with an Increased risk of atherosclerosis, thrombosis and stroke. Thiols also react with nitric oxide (NO, an endothelium-derived relaxing factor (EDRF) ), forming S-nitrosothiols that have been reported to have potent vasodilatory and antiplatelet effects and been expected to decrease adverse vascular effects of homocysteine. The present study was aimed to Investigate whether the S-nitrosation of homocysteine modulates the neurotoxic effects of homocysteine. An 18 hour-exposure of cultured rat cortical neurons to homocysteine ( >1 mM) resulted in a significant neuronal cell death. At comparable concentrations ( <10 mM), however, S-nitrosohomocysteine did not induce neuronal cell death. Furthermore, S-nitrosohomocysteirle partially blocked NMDA-mediated neurotoxicity. S-nitrosohomocysteine also decreased NMDA-mediated increases in intracellular calcium concentration. The present data indicate that in brain nitric oxide produced from neuronal and nonneuronal cells can modulate the potential, adverse properties of homocysteine.