• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.2
• /
• pp.145-153
• /
• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
• /
• 2001.07a
• /
• pp.913-916
• /
• 2001

From 1994 the cooperation between NEU of China and MJU of South Korea for study of ReBaCuO (Re=Rare earth elements) superconductors has been carried out. The progress has been got in following projects. Critical current density ($J_c$) of YBaCuO superconductor prepared by Melting Textured Growth (MTG) was improved. In the preparation of textured YBaCuO, 20 wt.% of YBaCuO 211 phase was added, which would be climactic for the microcracks in the textured YBaCuO. The effects of the 211 phase and Ag content on the superconductivity were studied and discussed in detail. The improved $J_c$ value was reached to 8$\times$10^4 A/cm^2 (77K,0T). Single phase $YbBa_{2}Cu_{3}O_{x}$ superconductor was sintered by the traditional powder metallurgical method, and its reaction process was studied. In recent years, NdBaCuO superconductor is being performed. The behavior of $Nd_{4}Ba_{2}Cu_{2}O_{10}$(Nd422 phase) and the solid solubility, x in the superconductor $Nd_{1+x}Ba_{2-x}Cu_{3}O_{y}$ by the heat treatment in the low oxygen partial pressure (1%) or Ar at $950{\circ}C$ were investigated. The zone-melting process was used to make oriented NdBaCuO superconductor in order to increase the critical current density.

• International Journal of Oral Biology
• /
• v.33 no.2
• /
• pp.59-64
• /
• 2008

This study was designed to investigate the changes in the properties of the neuronal setm cells or progenitor cells associated with age-related decline in neurogenesis of the hippocampal dentate gyrus (DG). Active whole cells cycle marker Ki67 (a marker of whole cell cycle)-positive and S phase marker bromodeoxyuridine (BrdU)-positive. Neural stem cells gradually were reduced in the hippocampal subgranular zone (SGZ) in an age-dependant manner after birth (from P1 month to P1 year). The ratio of BrdUpositivecells/Ki67-positive cells was gradually enhanced in an age-dependent manner. The ratio of Ki67-positive cells/accu-mulating BrdU-positive cells at 3 hrs after BrdU injection was injected once a day for consecutive 5 days gradually decreased during ageing. TUNEL- and caspase 3 (apoptotic terminal caspase)-positive cells gradually decreased in the dentate SGZ during ageing and immunohistochemical findings of glial fibrillary acid protein (GFAP) were not changed during ageing. NeuN, a marker of mature neural cells, and BrdU-double positive cells gradually decreased in an age-dependent manner but differentiating ratio and survival rate of cells were not changed at 4 wks after BrdU injection once a day for consecutive 5 days. The number of BrdU-positive cells migrated from the hippocampal SGZ into granular layer and its migration speed was gradually declined during ageing. These results suggest that the adult neurogenesis in the mouse hippocampal DG gradually decrease through reducing proliferation of neural stem cells accompanying with cells cycle change and reduced cells migration rather than changes of differentiation.

• Parasites, Hosts and Diseases
• /
• v.55 no.3
• /
• pp.267-285
• /
• 2017

Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted. The movement and motor coordination were investigated at week 2 post infection (PI) and week 3 PI in mice and rats, respectively. The cognitive impairs could be found in mice at week 2 PI but not in rats. The plaque-like lesion, perivascular cuffing of inflammatory cells, and dilated vessels within the cerebral cortex and hippocampus were more serious in mice than in rats at week 3 PI. Transcriptomic analysis showed activated extrinsic apoptotic pathway through increased expression of TNFR1 and caspase-8 in mice CNS. Immunohistochemical and double-labeling for NeuN and caspase-3 indicated the dramatically increased expression of caspase-3 in neuron of the cerebral cortex and hippocampus in mice but not in rats. Furthermore, western-blotting results showed high expression of cleaved caspase-3 proteins in mice but relatively low expression in rats. Thus, extrinsic apoptotic pathway participated in neuronal apoptosis might be the pathological basis of distinct behavioral dysfunctions in rodents with A. cantonensis infection. It provides the evidences of a primary molecular mechanism for the behavioral dysfunction and paves the ways to clinical diagnosis and therapy for A. cantonensis infection.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.14
• /
• pp.5977-5981
• /
• 2015

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.

• BMB Reports
• /
• v.53 no.4
• /
• pp.234-239
• /
• 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.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.1
• /
• pp.41-51
• /
• 2016

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activating TLR4-NF-${\kappa}B$ signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-${\kappa}B$ pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPS-induced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.

• The Korea Journal of Herbology
• /
• v.26 no.3
• /
• pp.75-82
• /
• 2011

Objectives : In this study, we evaluated the effect of Chungganhaeju-hwan(CGHJH) on hydrogen peroxide($H_2O_2$)-induced and ethanol(EtOH)-induced neuronal damage in vitro and in vivo, respectively. Methods:We carried out the anti-oxidant effects of CGHJH against hydrogen peroxide($H_2O_2$)-induced toxicity in HT22 and PC12 cells using thiazolyl blue tetrazolium bromide. Then, to investigate the protective effect on CGHJH against EtOH-induced memory impairment and hippocampal cell damage in male ICR mice, we performed novel object recognition test(NORT), and analysed the brain tissues after immunohistochemistry and western blotting. Results:CGHJH showed protective effect from $H_2O_2$-induced cell toxicity at doses of $1\sim100{\mu}g$/mL in both HT22 and PC12 cells. CGHJH had also recovery effect from EtOH-induced memory impairment in ICR mice from NORT and it protected hippocampal cells against EtOH toxicity in the result of cresyl violet and NeuN immunoreactivity. Conclusion : These results demonstrate that CGHJH has protective effect in neuronal cells against $H_2O_2$ and EtOH toxicities and this effect could be a main role of recovery effect on EtOH-induced memory loss.

• Koreanishche Zeitschrift fur Deutsche Sprachwissenschaft
• /
• v.5
• /
• pp.289-310
• /
• 2002

Die Arbeit versucht, den Textbegriff aus prototypentheoretischer Sicht neu zu orientieren. Damit wird unter Text immer eine monologisch geschriebene sprachliche $\"{A}u{\ss}erung$ aus mehreren $S\"{a}tzen$ verstanden. Die in de Beaugrande/Dressler(l98l) als wichtig bezeichnete Textmerkmale wird dann in Bezug auf Vater(1992), $L\"{o}tscher(1987)$ und Klein/von Stutterheim (1991) kritisch $gekl\"{a}rt$. Daraus ergibt sich eine merkmalsorientierte Textbestimmung: Ein Text ist eine abgeschlossene themenorientierte kommunikative Einheit in einem konkreten Kontext; er hat eine bestimmte kommunikative Funktion und $erf\"{u}llt\;koh\"{a}rente$ Bedingungen. Meine These ist: Typische Texte sind auf Mustern, $n\"{a}mlich$ auf Prototypen bezogen. Textmuster sind als Prototypen bezeichnet, die in unterschiedlichem $Ma\ss\;Spielraum\;f\"{u}r\;Variationen\;und\;Kreativit\"{a}t$ lassen. Textmuster sind zu beschreiben $\"{u}ber$ das Zusammenspiel von nichtsprachlichem Handlungstyp und sprachlicher Textsorte. Dieses Zusammenspiel yon Handlungsaspekten wird in prototypischer Weise mit bestimmten Textmerkmalen verbalisiert. Mit Textmusterbeschreibungen werden jeweils prototypische Exemplare beschrieben: die beste Exemplare, die klar als solehe erkennbar sind. Die Formulierung 'Es war einmal....'. ist $f\"{u}r\M\"{a}rchen$ zwar prototypische Anfangsform, aber sie wird nur in etwa einem drittel der $F\"{a}lle$ verwendet. Prototypische Textmustermerkmale sind also nicht obligatorisch. Das $hei{\ss}t$, dass die Realiseirungen je nach individueller bzw. kultureller Situation und damit verfolgtem Zweck variabel sind Damit habe ich mich am Beispiel der Textsorte $besch\"{a}ftigt$.

• Journal of Acupuncture Research
• /
• v.30 no.3
• /
• pp.1-13
• /
• 2013

Objectives : This study was performed to choose more effective neuro-protective acupuncture point and to verify the effect of acupuncture in promoting neurogenesis and angiogenesis as a result of its neuro-vasculo-regenerative effect in middle cerebral artery occlusion model in rats. Methods : By TTc staining we chose the most effective acupuncture point with neuro-protection. We randomly divided into four groups: Such as (1) sham group(with sham-operation), (2) sham+acupuncture group(with sham-operation), (3) middle cerebral artery occlusion group, (4) MCAO+AT group. Acupuncture procedure was performed for four days. Total RNA was extracted using TRIzol reagent, according to the manufacturer's instructions, and was purified using an RNAeasy mini kit. Immuno-histochemistry was performed using primary antibody mouse anti-BrdU, NeuN, Dcx, and VEGF. Results : We found that $ST_{36}$ had the more neuroprotective effect than $LI_{11}$ and $SP_3$. The microarray analysis revealed that 54 genes were more expressed neurogenesis pathway in MCAO+AT group compared with MCAO group(fold changes greater than or equal to twofold change). 11 genes were more expressed angiogenesis pathway. And 7 genes were more expressed VEGF pathway. Immuno-histochemistry revealed that cell proliferation, cell migration and cell maturation were increased. Conclusions : This study demonstrated that acupuncture on $ST_{36}$ had neuro-protective and neuro-restorative effect in ischemic brain injuries. And its mechanism might be related to promote neurogenesis and angiogenesis. These results suggest that acupuncture have potential benefits for the treatment of ischemic stroke.