Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels

Jeon, Seong Gak,Kim, Kyoung Ah,Chung, Hyunju,Choi, Junghyun,Song, Eun Ji,Han, Seung-Yun,Oh, Myung Sook,Park, Jong Hwan,Kim, Jin-il,Moon, Minho Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.8

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. However, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.

Visualization of Altered Hippocampal Connectivity in an Animal Model of Alzheimer’s Disease

Jeon, Seong Gak,Kim, Yong Jun,Kim, Kyoung Ah,Mook-Jung, Inhee,Moon, Minho Springer US 2018 Molecular neurobiology Vol.55 No.10

<P>Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline and neurodegeneration in the hippocampus. Despite the pathological importance of the hippocampal degeneration in AD, little topographical evidence exists of impaired hippocampal connectivity in patients with AD. To investigate the anatomical connections of the hippocampus, we injected the neurotracer 1,1′-dioctadecyl-3,3,3′3,3′-tetramethyl-indocarbocyanine perchlorate (DiI) into the hippocampi of 5XFAD mice, which were used as an animal model of AD. In wild-type controls, DiI-containing cells were found in the entorhinal cortex, medial septum, locus coeruleus, dorsal raphe, substantia nigra pars compacta, and olfactory bulb. Hippocampal inputs were decreased in multiple brain regions in the 5XFAD mice compared to wild-type littermate mice. These results are the first to reveal alterations at the cellular level in hippocampal connectivity in the brains of 5XFAD mice. These results suggest that anatomical mapping of hippocampal connectivity will elucidate new pathogenic mechanisms and therapeutic targets for AD treatment.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1007/s12035-018-0918-y) contains supplementary material, which is available to authorized users.</P>

Impaired Memory in OT-II Transgenic Mice Is Associated with Decreased Adult Hippocampal Neurogenesis Possibly Induced by Alteration in Th2 Cytokine Levels

Minho Moon,Seong Gak Jeon,Kyoung Ah Kim,Hyunju Chung,Junghyun Choi,Eun Ji Song,Seung-Yun Han,Myung Sook Oh,Jong-Hwan Park,Jin-il Kim 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.8

Recently, an increasing number of studies have focused on the effects of CD4+ T cell on cognitive function. How-ever, the changes of Th2 cytokines in restricted CD4+ T cell receptor (TCR) repertoire model and their effects on the adult hippocampal neurogenesis and memory are not fully understood. Here, we investigated whether and how the mice with restricted CD4+ repertoire TCR exhibit learning and memory impairment by using OT-II mice. OT-II mice showed decreased adult neurogenesis in hippocampus and short- and long- term memory impairment. Moreover, Th2 cytokines in OT-II mice are significantly increased in peripheral organs and IL-4 is significantly increased in brain. Finally, IL-4 treatment significantly inhibited the proliferation of cultured adult rat hippocampal neural stem cells. Taken together, abnormal level of Th2 cytokines can lead memory dysfunction via impaired adult neurogenesis in OT-II transgenic.

Plate Anchor의 인발거동에 관한 모형실험

김서성,이상덕,구자갑,전몽각,유건선,Kim, Seo Seong,Lee, Sang Duk,Koo, Ja Kap,Jeon, Mong Gak,Yoo, Keon Seon 대한토목학회 1994 대한토목학회논문집 Vol.14 No.5

앵커의 극한인발력을 결정하기 위해서는 인발에 의한 지반의 파괴기구를 정확하게 알아야 한다. 그러나 앵커의 인발저항에 영향을 끼치는 요소 중에서 묻힘비에 따른 파괴기구의 변화에 대한 기존의 연구가 미흡한 실정이다. 본 연구에서는 판앵커의 수직인발시 묻힘비에 따른 파괴가구의 변화를 보다 명확히 관찰하고, 지존의 극한인발력 산정식의 적용성을 판단하기 위하여 탄소봉으로 조성된 평면변행률상태의 지반에서 모형실험을 실시하였다. 그 결과로서, 얕은앵커상태와 깊은앵커상태일 때의 지반의 파괴특성을 명확히 구분할 수 있었으며, 깊은앵커의 극한인발력의 산정에 앞서 얕은앵커의 해석이 선행되어야 한다는 것이 증명되었다. For Determination of the ultimate uplift capacity, the failure mechanism of the foundation by uplift should be correctly known. However, studies on the variation of the failure mechanism with the embedment ratio of anchor plate among those factors governing the uplift resistance are scarce. In this study. in an attempt to observe more clearly the variation of the failure mechanism with embedment ratio and to check applicability of existing formulae for the ultimate uplift capacity. a model test was performed with ground made of carbon rods, simulating a plane strain conditions. As a result, failure characteristics of shallow and deep anchor conditions were clearly classified. It was found that the analysis of a shallow anchor should be made prior to determination of the ultimate uplift capacity of a deep anchor.

<i>Uncaria rhynchophylla</i> ameliorates amyloid beta deposition and amyloid beta-mediated pathology in 5XFAD mice

Shin, Soo Jung,Jeong, Yuon,Jeon, Seong Gak,Kim, Sujin,Lee, Seong-kyung,Choi, Hong Seok,Im, Cheong Su,Kim, Seong Hee,Kim, Soo Hwan,Park, Jae Ho,Kim, Jin-il,Kim, Jwa-Jin,Moon, Minho Elsevier 2018 Neurochemistry International Vol.121 No.-

<P><B>Abstract</B></P> <P>One of the pathological hallmarks of Alzheimer's disease (AD) is the abnormal aggregation of amyloid beta (Aβ) peptides. <I>Uncaria rhynchophylla</I> (UR), one of the <I>Uncaria</I> species, has long been used to treat neurodegenerative disease. In particular, it has been reported that UR inhibits aggregation of Aβ <I>in vitro.</I> However, little is known about the histological effects of UR treatment on Aβ pathology in AD animal models. In the present study, we investigated the effect of UR on Aβ aggregation, Aβ-mediated pathologies and adult hippocampal neurogenesis in the brain of 5XFAD mice. First, using the thioflavin T assay and amyloid staining, we demonstrated that UR treatment effectively inhibited Aβ aggregation and accumulation in the cortex and subiculum. Second, immunofluorescence staining showed that administration of UR attenuated gliosis and neurodegeneration in the subiculum and cortex. Third, UR treatment ameliorated impaired adult hippocampal neurogenesis. The present results indicate that UR significantly alleviates Aβ deposition and Aβ-mediated neuropathology in the brain in 5XFAD mice, suggesting the potency of UR as a preventive and therapeutic agent for AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Uncaria rhynchophylla</I> (UR) inhibited Aβ aggregation and accumulation. </LI> <LI> UR alleviated neuroinflammation induced by Aβ. </LI> <LI> Treatment of UR relieved synaptic and neuronal loss in AD mice. </LI> <LI> UR attenuated impaired hippocampal neurogenesis induced by Aβ. </LI> </UL> </P>

Jowiseungchungtang Inhibits Amyloid-β Aggregation and Amyloid-β-Mediated Pathology in 5XFAD Mice

Shin, Soo Jung,Jeong, Yu-on,Jeon, Seong Gak,Kim, Sujin,Lee, Seong-kyung,Nam, Yunkwon,Park, Yong Ho,Kim, Dabi,Lee, Youn Seok,Choi, Hong Seok,Kim, Jin-il,Kim, Jwa-Jin,Moon, Minho MDPI AG 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.12

<P>Alzheimer’s disease (AD) is a neurodegenerative disease, which is accompanied by memory loss and cognitive dysfunction. Although a number of trials to treat AD are in progress, there are no drugs available that inhibit the progression of AD. As the aggregation of amyloid-β (Aβ) peptides in the brain is considered to be the major pathology of AD, inhibition of Aβ aggregation could be an effective strategy for AD treatment. Jowiseungchungtang (JWS) is a traditional oriental herbal formulation that has been shown to improve cognitive function in patients or animal models with dementia. However, there are no reports examining the effects of JWS on Aβ aggregation. Thus, we investigated whether JWS could protect against both Aβ aggregates and Aβ-mediated pathology such as neuroinflammation, neurodegeneration, and impaired adult neurogenesis in 5 five familial Alzheimer’s disease mutations (5XFAD) mice, an animal model for AD. In an in vitro thioflavin T assay, JWS showed a remarkable anti-Aβ aggregation effect. Histochemical analysis indicated that JWS had inhibitory effects on Aβ aggregation, Aβ-induced pathologies, and improved adult hippocampal neurogenesis in vivo. Taken together, these results suggest the therapeutic possibility of JWS for AD targeting Aβ aggregation, Aβ-mediated neurodegeneration, and impaired adult hippocampal neurogenesis.</P>

C2 스타일의 아키텍쳐 기술을 지원하는 ADL 지원도구의 개발

신동익,노성환,최재각,전태웅,이승연,Sin, Dong-Ik,No, Seong-Hwan,Choe, Jae-Gak,Jeon, Tae-Ung,Lee, Seung-Yeon 한국정보처리학회 2001 정보처리학회논문지D Vol.8 No.6

최근, 소프트웨어의 재사용성, 생산성, 그리고 품질을 높이기 위한 방법으로서 컴포넌트 기반의 소프트웨어 개발(CBD:Component-Based Development) 방식이 빠르게 확산되고 있다. CBD를 효과적으로 수행하기 위해서는 응용 컴포넌트들이 서로 정확하게 결합하여 작동할 수 있는 아키텍쳐를 기반으로 하여 컴포넌트의 생성과 합성 작업이 이루어질 수 있어야 한다. 소프트웨어 아키텍쳐는 아키텍쳐 기술 언어(ADL:Architecture Description Language)를 사용하여 기술되어야 정확하고 엄밀한 아키텍쳐 모델링이 가능하다. 본 논문에서는 도메인 아키텍쳐 기반의 CBD에 효과적으로 사용될 수 있는 ADL 지원도구의 시스템 아키텍쳐를 제안하고, 제안한 시스템 아키텍쳐의 각 구성 요소들에 대하여 기술한다. 그리고 C2 스타일의 아키텍쳐 기술을 지원하는 UCI(University of California in Irvine)의 C2SADL을 변경하여 재정의한 ADL과 지원도구로서 개발 중인 ADL 지원도구의 설계 및 구현 방법을 기술한다. 본 연구팀이 개발 중인 ADL 지원도구는 본 논문에서 제안한 ADL 지원도구의 시스템 아키텍쳐의 일부 구성 요소들을 구현한다. Recently, component-based development (CBD) is rapidly spreading as a way of improving the reusability, productivity, and quality of software. For CBD to be effective in achieving such design objectives, the creation and integration of components must be based on a well-defined architecture that guides the correct composition and cooperation of application components. Software architecture must be described using an architecture description language (ADL) to ensure the correctness and preciseness of architecture models. In this paper, we propose the system architecture of an ADL tool set that can effectively support the use of CBD based on the domain architecture and we describe each component of the proposed system architecture. We also modify and redefine C2SADL that was developed to support the use of the description of C2 architectural style by UCI (University of California in Irvine) to facilitate the integration of separately described architecture models, and introduce the method of design and implementation of our ADL processor that partially implements the proposed ADL system architecture.

MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease

Jeong, Yu-on,Shin, Soo Jung,Park, Jun Yong,Ku, Bo Kyeong,Song, Ji Soo,Kim, Jwa-Jin,Jeon, Seong Gak,Lee, Sang Min,Moon, Minho MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.6

<P>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, neuroinflammation, and neuronal death. The primary pathogenic cause is believed to be the accumulation of pathogenic amyloid beta (Aβ) assemblies in the brain. Ghrelin, which is a peptide hormone predominantly secreted from the stomach, is an endogenous ligand for the growth hormone secretagogue-receptor type 1a (GHS-R1a). MK-0677 is a ghrelin agonist that potently stimulates the GHS-R1a ghrelin receptor. Interestingly, previous studies have shown that ghrelin improves cognitive impairments and attenuates neuronal death and neuroinflammation in several neurological disorders. However, it is unknown whether MK-0677 can affect Aβ accumulation or Aβ-mediated pathology in the brains of patients with AD. Therefore, we examined the effects of MK-0677 administration on AD-related pathology in 5XFAD mice, an Aβ-overexpressing transgenic mouse model of AD. MK-0677 was intraperitoneally administered to three-month-old 5XFAD mice. To visualize Aβ accumulation, neuroinflammation, and neurodegeneration, thioflavin-S staining and immunostaining with antibodies against Aβ (4G8), ionized calcium-binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), neuronal nuclear antigen (NeuN), and synaptophysin were conducted in the neocortex of 5XFAD and wild-type mice, and to evaluate changes of phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (pCREB) levels, immunostaining with antibody against pCREB was performed in dentate gyrus of the hippocampus of 5XFAD and wild-type mice. The histological analyses indicated that MK-0677-treated 5XFAD mice showed reduced Aβ deposition, gliosis, and neuronal and synaptic loss in the deep cortical layers, and inhibited the decrement of pCREB levels in dentate gyrus of the hippocampus compared to vehicle-treated 5XFAD mice. Our results showed that activation of the ghrelin receptor with MK-0677 inhibited the Aβ burden, neuroinflammation, and neurodegeneration, which suggested that MK-0677 might have potential as a treatment of the early phase of AD.</P>