• Molecules and Cells
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• v.40 no.7
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• pp.485-494
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• 2017

Oleanolic acid (OA) has neurotrophic effects on neurons, although its use as a neurological drug requires further research. In the present study, we investigated the effects of OA and OA derivatives on the neuronal differentiation of rat hippocampal neural progenitor cells. In addition, we investigated whether the class II histone deacetylase (HDAC) 5 mediates the gene expression induced by OA. We found that OA and OA derivatives induced the formation of neurite spines and the expression of synapse-related molecules. OA and OA derivatives stimulated HDAC5 phosphorylation, and concurrently the nuclear export of HDCA5 and the expression of HDAC5 target genes, indicating that OA and OA derivatives induce neural differentiation and synapse formation via a pathway that involves HDAC5 phosphorylation.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.2
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• pp.59-64
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• 2006

The effects of $Zn^{2+}$ on spontaneous glutamate and GABA release were tested in mechanically dissociated rat CA3 pyramidal neurons which retained functional presynaptic nerve terminals. The spontaneous miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs, respectively) were pharmacologically isolated and recorded using whole-cell patch clamp technique under voltage-clamp conditions. $Zn^{2+}$ at a lower concentration $(30{\mu}M)$ increased GABAergic mIPSC frequency without affecting mIPSC amplitude, but it decreased both mIPSC frequency and amplitude at higher concentrations $({\ge}300{\mu}M)$. In contrast, $Zn^{2+}$ (3 to $100{\mu}M$) did not affect glutamatergic mEPSCs, although it slightly decreased both mIPSC frequency and amplitude at $300{\mu}M$ concentration. Facilitatory effect of $Zn^{2+}$ on GABAergic mIPSC frequency was occluded either in $Ca^{2+}$-free external solution or in the presence of $100{\mu}M$ 4-aminopyridine, a non-selective $K^{+}$ channel blocker. The results suggest that $Zn^{2+}$ at lower concentrations depolarizes GABAergic nerve terminals by blocking $K^{+}$ channels and increases the probability of spontaneous GABA release. This $Zn^{2+}$-mediated modulation of spontaneous GABAergic transmission is likely to play an important role in the regulation of neuronal excitability within the hippocampal CA3 area.

• BMB Reports
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• v.50 no.3
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• pp.109-110
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• 2017

The nature of encoded information in neural circuits is determined by neuronal firing patterns and frequencies. This paper discusses the molecular identity and cellular mechanisms of spike-frequency adaptation in the central nervous system (CNS). Spike-frequency adaptation in thalamocortical (TC) and CA1 hippocampal neurons is mediated by the $Ca^{2+}$-activated $Cl^-$ channel (CACC) anoctamin-2 (ANO2). Knockdown of ANO2 in these neurons results in increased number of spikes, in conjunction with significantly reduced spike-frequency adaptation. No study has so far demonstrated that CACCs mediate afterhyperpolarization currents, which result in the modulation of neuronal spike patterns in the CNS. Our study therefore proposes a novel role for ANO2 in spike-frequency adaptation and transmission of information in the brain.

• Proceedings of the Ginseng society Conference
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• 2002.10a
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• pp.531-544
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• 2002

Ginseng is the best known and most popular herbal medicine used worldwide. Ameliorating effects of ginseng were observed on the models of scopolamine-induced, aged or hippocampal lesioned learning and memory deficits. Further beneficial effects of ginseng were observed on neuronal cell death associated with ischemia or glutamate toxicity. In spite of these beneficial effects of ginseng on the CNS, little scientific evidence shows at the cellular level. In the present study, we have employed cultures of rat hippocampal neurons and examined the direct modulation of ginseng on NMDA receptor-induced changes in $[Ca^{2+}]_i$ and -gated currents using fura-2-based digital imaging and perforated whole-cell patch-clamp techniques, respectively. We found that ginseng total saponins inhibited NMDA-induced but less effectively glutamate-induced increase in $[Ca^{2+}]_i$ Ginseng total saponins also modulated $Ca^{2+}$ transients evoked by depolarization with 50 mM KCI along with its own effects on $[Ca^{2+}]_i$. Among ginsenosides tested, ginsenoside $Rg_3$ was found to be the most potent component for ginseng actions on NMDA receptors. Furthermore, we examined the inhibitory effects ofbiotransformants of ginsenosides on NMDA receptor using purified stereoisomers of ginsenosides. 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_3$, produced the strongest inhibition while 20(S)-ginsenoside $Rh_1$ and Compound K produced the moderate inhibition on NMDA-induced increase in $[Ca^{2+}]_i$. The data obtained suggest that the inhibition of NMDA receptors by ginseng, in particular by 20(S)-ginsenoside $Rg_3$ and its metabolite, 20(S)-ginsenoside $Rh_2$, could be one of mechanisms for ginsengmediated neuroprotective actions.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.4
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• pp.281-285
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• 2012

A previous animal study has shown the effects of erythropoietin (EPO) and its non-erythropoietic carbamylated derivative (CEPO) on neurogenesis in the dentate gyrus. In the present study, we sought to investigate the effect of EPO on adult hippocampal neurogenesis, and to compare the ability of EPO and CEPO promoting dendrite elongation in cultured hippocampal neural progenitor cells. Two-month-old male BALB/c mice were given daily injections of EPO (5 U/g) for seven days and were sacrificed 12 hours after the final injection. Proliferation assays demonstrated that EPO treatment increased the density of bromodeoxyuridine (BrdU)-labeled cells in the subgranular zone (SGZ) compared to that in vehicle-treated controls. Functional differentiation studies using dissociated hippocampal cultures revealed that EPO treatment also increased the number of double-labeled BrdU/microtubulea-ssociated protein 2 (MAP2) neurons compared to those in vehicle-treated controls. Both EPO and CEPO treatment significantly increased the length of neurites and spine density in MAP2(+) cells. In summary, these results provide evidences that EPO and CEPO promote adult hippocampal neurogenesis and neuronal differentiation. These suggest that EPO and CEPO could be a good candidate for treating neuropsychiatric disorders such as depression and anxiety associated with neuronal atrophy and reduced hippocampal neurogenesis.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.301-309
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• 2018

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

• The Korea Journal of Herbology
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• v.30 no.3
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• pp.49-54
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• 2015

Objectives : This study investigated the neuroprotective effect of Gastodia Rhizoma-gamibang (GG) water extracts against scopolamine-induced neurotoxicity in the hippocampus of male Sprague-Dawley rats. Methods : The animals were divided into five different groups with six animals per each group. The normal group (Nor) was administered with saline, while the control group (Con) was administered with saline after scopolamine treatment. The experimental group (Exp) was administered orally GG extracts at doses of 200 mg/kg (GG1 group), 400 mg/kg (GG2 group), 1000 mg/kg (GG5 group) for 30 day after scopolamine treatment. Results : From a light microscopy study, the nuclei of neurons and glial cells in the hippocampus were more shrunken or condensed in the 30 day control group compared with normal group. In the experimental groups, proportional to the dose, recovered from neurotoxicity induced by scopolamine. The control group, the density of hippocampal neurons were reduced 17-20% compared to normal group. The densities of neurons from the CA1, and CA3 area of the hippocampus in the GG1, GG2 and GG5 groups significantly increased compared with the Con. In the experimental group, neuronal cells are recovered from scopolamine-induced damage. A number of glial cells are observed increase from GG2 and GG5 groups. The PAS-positive materials in the tissues hippocampus), was lower in the Exp than the Con. Conclusions : The present study demonstrates that Gastodia Rhizoma-gamibang extract reduces neuronal damage in the hippocampus of scopolamin-induced impairment mice.

• Journal of Life Science
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• v.26 no.4
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• pp.475-483
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• 2016

The current study was conducted to evaluate beneficial effects of a new formula (CWC-9) using four traditional Oriental medicinal herbs, Cynanchum wilfordii, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, on hippocampal cells and memory function. To examine the neuroprotective effects of a new four-herb extract, cell viability, cytotoxicity, and reactive oxygen species (ROS) assays were performed in HT22 cells and behavioral tests (Morris water maze and passive avoidance retention), Western blot, and immunohistochemistry were performed in a mouse model of focal cerebral ischemia. In HT22 hippocampal cells, pretreatment with CWC-9 resulted in significantly reduced glutamate-induced cell death with suppression of ROS accumulation caused by glutamate. In a mouse model of focal cerebral ischemia, we observed significant improvement of spatial and short-term memory function by treatment with CWC-9. Phosphorylated p38 mitogen-activated protein kinases (MAPK) in hippocampus of ischemic mice were decreased by treatment with CWC-9, but phosphorylated phosphatidylinositol-3 kinase (PI3K) and cAMP response element binding protein (CREB) were significantly enhanced. By immunohistochemical analysis, we confirmed higher expression of phosphorylation of CREB in the hippocampal neurons of CWC-9 treated mice. These results suggest that new multi-herb formula CWC-9 mainly exerted beneficial effects on cognitive function through regulation of neuro-protective signaling pathways associated with CREB.

• Molecules and Cells
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• v.26 no.2
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• pp.186-192
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• 2008

NELL2, a neural tissue-enriched protein, is produced in the embryo, and postembryonically in the mammalian brain, with a broad distribution. Although its synthesis is required for neuronal differentiation in chicks, not much is known about its function in the adult mammalian brain. We investigated the distribution of NELL2 in various regions of the adult rat brain to study its potential functions in brain physiology. Consistent with previous reports, NELL2-immunoreactivity (ir) was found in the cytoplasm of neurons, but not in glial fibrillary acidic protein (GFAP)-positive glial cells. The highest levels of NELL2 were detected in the hippocampus and the cerebellum. Interestingly, in the cerebellar cortex NELL2 was observed only in the GABAergic Purkinje cells not in the excitatory granular cells. In contrast, it was found mainly in the hippocampal dentate gyrus and pyramidal cell layer that contains mainly glutamatergic neurons. In the dentate gyrus, NELL2 was not detected in the GFAP-positive neural precursor cells, but was generally present in mature neurons of the subgranular zone, suggesting a role in this region restricted to mature neurons.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.328-337
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• 2016

We examined whether wogonin (WO) improved hippocampal neuronal activity, behavioral alterations and cognitive impairment, in rats induced by administration of trimethyltin (TMT), an organotin compound that is neurotoxic to these animals. The ability of WO to improve cognitive efficacy in the TMT-induced neurodegenerative rats was investigated using a passive avoidance test, and the Morris water maze test, and using immunohistochemistry to detect components of the acetylcholinergic system, brain-derived neurotrophic factor (BDNF), and cAMP-response element-binding protein (CREB) expression. Rats injected with TMT showed impairments in learning and memory and daily administration of WO improved memory function, and reduced aggressive behavior. Administration of WO significantly alleviated the TMT-induced loss of cholinergic immunoreactivity and restored the hippocampal expression levels of BDNF and CREB proteins and their encoding mRNAs to normal levels. These findings suggest that WO might be useful as a new therapy for treatment of various neurodegenerative diseases.