• Title/Summary/Keyword: Neurodegenerative Disorders

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Metabolic Topography of Parkinsonism

  • Kim, Jae-Seung
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.2
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    • pp.141-151
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    • 2007
  • Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson diorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkisonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, an assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of parkisonism.

Effects of Resveratrol and trans-3,5,4'-Trimethoxystilbene on Glutamate-Induced Cytotoxicity, Heme Oxygenase-1, and Sirtuin 1 in HT22 Neuronal Cells

  • Kim, Dae-Won;Kim, Young-Mi;Kang, Sung-Don;Han, Young-Min;Pae, Hyun-Ock
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.306-312
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    • 2012
  • Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamate-induced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotection afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.

Radioactive cDNA microarray in Neurospsychiatry (신경정신 의학분야의 방사성동위원소 표지 cDNA 마이크로어레이)

  • Choe, Jae-Gol;Shin, Kyung-Ho;Lee, Min-Soo;Kim, Meyoung-Kon
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.1
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    • pp.43-52
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    • 2003
  • Microarray technology allows the simultaneous analysis of gene expression patterns of thousands of genes, in a systematic fashion, under a similar set of experimental conditions, thus making the data highly comparable. In some cases arrays are used simply as a primary screen loading to downstream molecular characterization of individual gene candidates. In other cases, the goal of expression profiling is to begin to identify complex regulatory networks underlying developmental processes and disease states. Microarrays were originally used with ceil lines or other simple model systems. More recently, microarrays have been used in the analysis of more complex biological tissues including neural systems and the brain. The application of cDNA arrays in neuropsychiatry has lagged behind other fields for a number of reasons. These include a requirement for a large amount of input probe RNA In fluorescent-glass based array systems and the cellular complexity introduced by multicellular brain and neural tissues. An additional factor that impacts the general use of microarrays in neuropsychiatry is the lack of availability of sequenced clone sets from model systems. While human cDNA clones have been widely available, high qualify rat, mouse, and drosophilae, among others are just becoming widely available. A final factor in the application of cDNA microarrays in neuropsychiatry is cost of commercial arrays. As academic microarray facilitates become more commonplace custom made arrays will become more widely available at a lower cost allowing more widespread applications. in summary, microarray technology is rapidly having an impact on many areas of biomedical research. Radioisotope-nylon based microarrays offer alternatives that may in some cases be more sensitive, flexible, inexpensive, and universal as compared to other array formats, such as fluorescent-glass arrays. In some situations of limited RNA or exotic species, radioactive membrane microarrays may be the most practical experimental approach in studying psychiatric and neurodegenerative disorders, and other complex questions in the brain.

Antioxidant and Neuronal cell protective effects of Stachys sieboldii Miq. according to drying methods (건조방법에 따른 초석잠(Stachys sieboldii Miq.)의 항산화 활성 및 신경세포 보호효과)

  • Oh, Hee-Kyung
    • Journal of the Korean Applied Science and Technology
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    • v.35 no.4
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    • pp.1320-1326
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    • 2018
  • This study investigated the antioxidant and neuronal cell protective effects of activity of water and 70% ethanol extracts from Stachys sieboldii Miq. according to different drying method(hot air drying and freeze-drying). The total flavonoid and total polyphenol content in water extracts was significantly higher after freeze-drying compared to hot air drying(p<0.05). DPPH and ABTS radical scavenging were increased in a dose-dependent manner. The DPPH and ABTS radical scavenging activity of water extract were significantly higher after free-drying compared to hot air drying(p<0.05). In a cell viability using MTT, the water extract according to hot air drying and freeze-drying of Stachys sieboldii Miq. showed protective effect against H2O2-induced nurotoxicity. The results suggest that the water extracts of Stachys sieboldii Miq. after freeze-drying has antioxidant activities and may be useful for neurodegenerative disorders.

Neuroprotective Effects of Schisandra chinensis and Ribes fasciculatum Extract on Hydrogen Peroxide-Mediated Oxidative Stress in Neuroblastic SH-SY5Y Cell Line (과산화수소로 유도된 SH-SY5Y 신경세포 사멸에 대한 오미자·칠해목 추출혼합물의 보호효과)

  • Park, Eun-kuk;Han, Kyung-Hoon;Lee, Seung-Hee;Kim, Nam-Ki;Bae, Mun-Hyoung;Seo, Young-Ha;Yong, Yoon-joong;Jeong, Seon-Yong;Choi, Chun-Whan
    • The Korean Journal of Food And Nutrition
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    • v.31 no.6
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    • pp.865-872
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    • 2018
  • In neuronal cell deaths, oxidative stress is normally implicated with a most of these deaths occurring in neurodegenerative disorders such as the Alzheimer's and Parkinson's diseases. In this study, the neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts on hydrogen peroxide ($H_2O_2$)-induced oxidative stress in neuroblastic cell line were investigated. For an hour, hydrogen peroxide of $100{\mu}M$ concentration, was induced on neuroblastic cells, causing apoptic cell death. For the neuroprotection, a sample of neuroblastic cells had been pre-treated with SC and RF extracts for 24 hours before application of the hydrogen peroxide. No neurotoxic effects were observed in the cells that had been treated by SC and RF. This prove that the treatment of SC and RF extract prevented apoptotic cell death of neuroblastic cell line exposed to oxidative injury. In addition, applying both SC and RF extracts at a 7:3 ratio increased the neuronal cell survival rate, compared to individual treatments of SC and RF extract. This study suggests that SC and RF extracts may be potential therapeutic agents for the prevention of neuronal cell death.

Considerations for the effects of antioxidant phytochemicals on human health (산화방지제 파이토케미컬이 건강에 미치는 영향에 대해 고려할 점)

  • Kim, Dae-Ok;Lee, Chang Y.
    • Korean Journal of Food Science and Technology
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    • v.53 no.2
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    • pp.111-114
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    • 2021
  • Phytochemicals in fruits, vegetables, cereals, and nuts, advertised as "antioxidants", combat undesirable effects of reactive oxygen species (ROS) in the body. These undesirable effects include cancer, cardiovascular diseases, and neurodegenerative disorders. Although ROS were initially considered to be primarily damaging agents, ROS have been discovered to play a role in signaling immune and other physiological responses in recent years. Several studies have demonstrated that ROS act as essential signaling molecules to promote metabolic health. Therefore, the overall advantage of the interference of ROS signals by antioxidants could be questionable. Future research is required to understand the implications of the application of phytochemicals in functional foods and supplements for health benefits on ROS levels in the body. This study describes the new roles of ROS and hormesis of various phytochemicals to provide a possible research guideline to food and nutrition scientists.

Neuroprotective effects of Paeonia lactiflora and its active compound paeoniflorin against Aβ25-35-induced neurotoxicity in SH-SY5Y cells

  • Nam, Mi Na;Kim, Ji-Hyun;Lee, Ah Young;Cho, Eun Ju
    • Journal of Applied Biological Chemistry
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    • v.64 no.2
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    • pp.105-112
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    • 2021
  • Excessive accumulation of the amyloid beta (Aβ) peptide has been implicated in the pathogenesis of Alzheimer's disease (AD). Paeonia lactiflora (PL) has been used in treatments of several conditions such as inflammation, arthritis, and cognitive impairment. The purpose of this study was to investigate the neuroprotective effect and mechanisms of PL and its active compound, paeoniflorin (PF), on Aβ25-35-induced neurotoxicity in SH-SY5Y cells. We evaluated cell viability, lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production. Furthermore, underlying mechanism of PL and PF on the regulation of amyloidogenic pathway was analyzed by Western blotting. In our results, Aβ25-35-induced neuronal cell loss was observed, whereas treatment with PL (10, 50, and 100 ㎍/mL) and PF (1, 5, and 10 ㎍/mL) significantly elevated the cell viability, and decreased LDH release and ROS production. In addition, exposure of SH-SY5Y cells to Aβ25-35 significantly increased the protein levels of amyloid precursor protein (APP)-C-terminal fragment β, β-site APP-cleaving enzyme, and presenilin-1 and -2. However, treatment with PL and PF inhibited the amyloidogenic pathway via the down-regulation of those protein expressions. Taken together, our results indicate that PL, and its active compound PF, could protect SH-SY5Y cells against Aβ25-35-induced cell neurotoxicity by attenuating LDH release and ROS production, and these effects may be attributed to regulation of amyloidogenic pathway-related protein expression. In conclusion, PL and PF could be a potential to prevent neurodegenerative disorders such as AD.

Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice

  • Kim, Taewoo;Jeon, Jeha;Park, Jin-Sun;Park, Yeongwon;Kim, Jooeui;Noh, Haneul;Kim, Hee-Sun;Seo, Hyemyung
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.483-491
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    • 2021
  • Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

Potential application of herbal medicine treatment based on pattern identification for canine cognitive dysfunctional syndrome: a comparative analysis of Korea medicine therapy for patients with dementia (반려견 인지기능장애증후군에 대한 한의 진단 및 한약치료 적용 가능성 고찰: 치매환자 국내한의치료기술과 비교 분석)

  • Jung, Kyungsook;Zhao, HuiYan;Choi, Yujin;Jang, Jung-Hee
    • Korean Journal of Veterinary Research
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    • v.62 no.3
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    • pp.25.1-25.9
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    • 2022
  • Canine cognitive dysfunction syndrome (CDS) is a neurodegenerative disease that causes cognitive and behavioral disorders and reduces the quality of life in dogs and their guardians. This study reviewed the complementary and alternative medicine (CAM) for CDS and compared the diagnosis and therapy of CAM between CDS in canines and dementia in humans. The evaluation tools for the diagnosis of CDS and dementia were similar in the neurological and neuropsychiatric examinations, daily life activity, cognitive tests, and neuroimaging, but the evaluation for dementia was further subdivided. In CAM, pattern identification is a diagnostic method for accurate, personalized treatment, such as herbal medicine. For herbal medicine treatment of cognitive impairment in canines and humans, a similar pattern identification classified as deficiency (Qi, blood, and Yin) and Excess (phlegm, Qi stagnation, and blood stasis) is being used. However, the veterinary clinical basis for verifying the efficacy and safety of CAM therapies for CDS is limited. Therefore, based on CAM evidence in dementia, it is necessary to establish CDS-targeted CAM diagnostic methods and therapeutic techniques considering the anatomical, physiological, and pathological characteristics of dogs.

Korean Red Ginseng extract ameliorates demyelination by inhibiting infiltration and activation of immune cells in cuprizone-administrated mice

  • Min Jung Lee;Jong Hee Choi;Tae Woo Kwon;Hyo-Sung Jo;Yujeong Ha;Seung-Yeol Nah;Ik-Hyun Cho
    • Journal of Ginseng Research
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    • v.47 no.5
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    • pp.672-680
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    • 2023
  • Background: Korean Red Ginseng (KRG), the steamed root of Panax ginseng, has pharmacological activities for immunological and neurodegenerative disorders. But, the role of KRGE in multiple sclerosis (MS) remains unclear. Purpose: To determine whether KRG extract (KRGE) could inhibit demyelination in corpus callosum (CC) of cuprizone (CPZ)-induced murine model of MS Methods: Male adult mice were fed with a standard chow diet or a chow diet supplemented with 0.2% (w/w) CPZ ad libitum for six weeks to induce demyelination while were simultaneously administered with distilled water (DW) alone or KRGE-DW (0.004%, 0.02 and 0.1% of KRGE) by drinking. Results: Administration with KRGE-DW alleviated demyelination and oligodendrocyte degeneration associated with inhibition of infiltration and activation of resident microglia and monocyte-derived macrophages as well as downregulation of proinflammatory mediators in the CC of CPZ-fed mice. KRGE-DW also attenuated the level of infiltration of Th1 and Th17) cells, in line with inhibited Mrna expression of IFN-γ and IL-17, respectively, in the CC. These positive effects of KRGE-DW mitigated behavioral dysfunction based on elevated plus maze and the rotarod tests. Conclusion: The results strongly suggest that KRGE-DW may inhibit CPZ-induced demyelination due to its oligodendroglial protective and anti-inflammatory activities by inhibiting infiltration/activation of immune cells. Thus, KRGE might have potential in therapeutic intervention for MS.