• 제목/요약/키워드: Brain-derived neurotrophic factor(BDNF)

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노르아드레날린성 신경세포에서의 BDNF 생산 증진 물질 탐색 (Screening of Potential Compounds Promoting BDNF Production in Noradrenergic Locus Coeruleus Neurons)

  • 전홍성
    • KSBB Journal
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    • 제18권3호
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    • pp.207-210
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    • 2003
  • Locus coeruleus (LC)에는 전체 노르아드레날린성 뉴런의 절반 가량이 모여 있는데, 여기서 노르아드레날린성 뉴런이 뇌의 거의 모든 부위로 신경자극을 보내게 된다. LC는 알츠하이머병, 파킨슨병, 헌팅턴병 같은 여러 가지 신경퇴행성 질환에서 공통적으로 타격을 받는 주요 부위이다. 뇌 유래 신경영양인자, BDNF가 LC 노르아드레날린성 뉴런을 포함한 중추신경계 뉴런들의 분화와 신경세포 생존에 중요한 조절자로 작용한다. 본 연구에서는 LC 노르아드레날린성 신경세포에서 여러 가지 작은 분자들과 성장인자들이 BDNF 생산을 촉진할 수 있는지를 조사하였다. 실험에 사용한 분자들로는 neuropeptides, cytokines, 성장인자, 신경전달물질들과 세포내 신호전달물질들이 포함되었다. 여러 가지 작은 분자들과 성장인자들 중에서 FGF8b, BMP-4, forskolin 그리고 dibutyrl cGMP가 LC 노르아드레날린성 뉴런에서 BDNF 분비를 뚜렷하게 증대시킨 것으로 판명되었다. 특히, BMP-4는 BDNF 생산을 2.5배 이상 증가시켰다. LC 노르아드레날린성 뉴런에서 BDNF를 증가시킨 물질들은 여러 가지 신경퇴행성 질환에서 신경세포가 손실되는 것을 막거나 지연시킬 수 있을 것이므로, 치료제나 증상완화제로서의 가능성이 높다.

전침자극과 트레드밀운동이 허혈성 뇌졸중 백서모델의 근위축 및 BDNF 발현에 미치는 영향 (Effects of Electroacupuncture and Treadmill Exercise on Muscle Atrophy and BDNF on the Ischemic Stroke Model of Rats)

  • 유영대;민순규;김기도;김계엽;심재환
    • 한국전문물리치료학회지
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    • 제14권1호
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    • pp.1-10
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    • 2007
  • This study was designed to examine the effects of electroacupuncture and treadmill exercise on the improvement of muscle atrophy and Brain-Derived Neurotrophic Factor (BDNF) expression in an ischemic stroke model induced by middle cerebral artery occlusion. This study selected 120 Sprangue-Dawley rats, divided them into six groups, and assigned 5 rats to each group. Experiments were conducted for 1, 3 days and 1, 8 weeks, respectively. In each group, changes in weight of muscle and relative muscle of tibialis anterior muscle, histologic observations, and BDNF expression were observed and analyzed. For the changes in muscle weight of unaffected and affected sides of tibialis anterior, muscle atrophy was expressed in an affected side 3 days after ischemic stroke was induced. There was a statistically significant difference in Group VI 1 and 8 weeks after ischemic stroke was induced, compared to Group II (p<.05). For the changes in relative muscle weight of unaffected and affected sides of tibial anterior muscle, there was significant decrease in each group 3 days after ischemic stroke was induced, compared to Group I, while there was a statistically significant increase in Group VI 1 week after ischemic stroke was induced, compared to Group II (p<.05). For neurologic exercise behavior test, Group VI generally had the highest score, compared to other groups. The results of the behavior test suggests that 8 weeks after ischemic stroke was induced, Group VI improved in degeneration and inflammation of muscle fiber and decreased in destruction of nerve cells and cerebral infarction, thus indicating a similar state of muscle fiber and brain tissue in Group I. In immunohistochemical observations, Group 1 week showed increase in BDNF. Based on these results, electroacupuncture and treadmill exercise may improve muscle atrophy and change in BDNF expression of ischemic stroke rats and contribute to the improvement of exercise function.

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Bacopa monnieri extract improves novel object recognition, cell proliferation, neuroblast differentiation, brain-derived neurotrophic factor, and phosphorylation of cAMP response element-binding protein in the dentate gyrus

  • Kwon, Hyun Jung;Jung, Hyo Young;Hahn, Kyu Ri;Kim, Woosuk;Kim, Jong Whi;Yoo, Dae Young;Yoon, Yeo Sung;Hwang, In Koo;Kim, Dae Won
    • Laboraroty Animal Research
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    • 제34권4호
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    • pp.239-247
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    • 2018
  • Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.

강도별 유산소운동이 중년여성의 레닌-알도스테론, 신경전달물질 및 인지기능, 작업기억의 변화에 관한 연구 (The Study of Change in Renin-Aldosterone, Neurotransmitters, Cognitive Function and Working Memory in Middle Aged Women by Intensities Aerobic Exercise)

  • 조원제
    • 한국체육학회지인문사회과학편
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    • 제55권2호
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    • pp.603-615
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    • 2016
  • 본 연구는 건강한 중년여성 28명을 대상으로 강도별 유산소운동을 12주간 주 3회로 실시하여 혈압, 레닌-알도스테론계, 신경전달물질 및 인지기능, 작업기억의 변화와 처치 후 인지기능에 영향을 미치는 요인을 분석하고자 실시하였다. 모집된 대상자를 통제집단 9명, 중강도 유산소운동집단 10명(50%V02max), 고강도 유산소운동집단 9명(70%V02max)으로 구분하여 처치 전과 후 반복측정 분산분석과 다중회귀분석을 실시한 결과 다음과 같은 결과가 나타났다. 중강도 유산소운동은 레닌, BDNF, 인지기능과 작업기억을 증가시키고, 알도스테론, 안지오텐신II, 알도스테론-레닌 비율을 감소시켰다. 고강도 유산소운동은 BDNF, 인지기능, 작업기억을 증가시키고 수축기혈압을 감소시켰다. 또한 강도별 유산소운동 후 인지기능에 미치는 요인을 회귀분석한 결과 중강도 유산소운동은 이완기혈압, 레닌-알도스테론 비율의 감소와 작업기억, BDNF의 증가가 인지기능에 영향을 미쳤고, 고강도 유산소운동은 작업기억 BDNF, 세로토닌의 증가가 인지기능에 영향을 미쳤다. 따라서 중강도 이상의 유산소운동은 중년여성의 인지기능 및 작업기억을 향상시키는 것을 알 수 있었다. 또한 인지기능 향상에 영향을 미치는 대사적 요인으로 중강도 유산소운동은 레닌-알도스테론 조절과 작업기억이었고 고강도 유산소운동은 신경전달물질과 작업기억으로 나타났다.

BDNF Promotes Neurite Growth and Survival of Antennal Lobe Neurons from the Silk Moth Bombyx mori in vitro

  • Kim, Jin-Hee;Sung, Dong-Kyung;Park, Chan-Woo;Kim, Kang-Min;Park, Hun-Hee;Kim, Hak-Ryul;Lee, Bong-Hee
    • 한국잠사학회:학술대회논문집
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    • 한국잠사학회 2003년도 International Symposium of Silkworm/Insect Biotechnology and Annual Meeting of Korea Society of Sericultural Science
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    • pp.99-99
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    • 2003
  • Brain-derived neurotrophic factor (BDNF) induced a significant neurite extension of antennal lobe (AL) neurons from the silk moth Bombyx mori in culture on lamini/ concanavalin A-coated dishes, in comparison with smaller effect of 20-hydroxyecdy-sone (20-HE). But the effect fur neurite extension by 5-hydroxytryptamine (5-HT) could not be found. A significant increase in the number of new primary branches from the principal neurites of AL neurons was also shown in culture with BDNF and 5-HT, but not with 20-HE. (omitted)

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Alpha-Asarone, a Major Component of Acorus gramineus, Attenuates Corticosterone-Induced Anxiety-Like Behaviours via Modulating TrkB Signaling Process

  • Lee, Bombi;Sur, Bongjun;Yeom, Mijung;Shim, Insop;Lee, Hyejung;Hahm, Dae-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권3호
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    • pp.191-200
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    • 2014
  • We investigated the anxiolytic-like activity of ${\alpha}$-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

LPS에 의해 유도된 인지기능 손상모델에 대한 천마 추출물의 방어효과 (Protective Effect of Gatrodiae Rhizoma Extracts on the LPS-Induced Cognitive Impairment Model)

  • 권강범;김하림;김예슬;박은희;강형원;류도곤
    • 동의신경정신과학회지
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    • 제33권3호
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    • pp.277-285
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    • 2022
  • Objectives: Gastrodia elata (GE) has been used to treat cognition impairment, including Alzheimer's disease (AD) in Korea. The purpose of this study was to investigate the effects of GE water extracts (GEE) on the lipopolysaccharide (LPS)-induced AD model in mice. (Aβ). Methods: We classified six groups as follow; group 1: control (CON), group 2: LPS (0.5 mg/kg/day, four times), group 3: 4 mg/kg donepezil (DP), group 4: 100 mg/kg GEE+LPS, group 5: 200 mg/kg GEE+LPS, group 6: 500 mg/kg GEE+LPS. Results: We found that GEE has an effect that inhibits decrease of discrimination index in object recognition test, as well as spontaneous alteration in the Y-maze test by LPS. Treatment with LPS increased amlyloid-β (Aβ) concentration, and decreased brain-derived neurotrophic factor (BDNF) in cerebral cortex of mice. However, GEE significantly protected against LPS-induced Aβ and BDNF changes. Our findings also showed that the inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β)] mRNA and protein were up-regulated by the LPS injection. But GEE significantly suppressed LPS-induced inflammatory cytokines increase in a dose-dependent manner. Conclusions: This study suggests that the GEE may be an effective AD therapeutic agent, in treating neurodegenerative diseases including AD.

Synergistic Increase of BDNF Release from Rat Primary Cortical Neuron by Combination of Several Medicinal Plant-Derived Compounds

  • Jeon, Se-Jin;Bak, Hae-Rang;Seo, Jung-Eun;Kwon, Kyung-Ja;Kang, Young-Sun;Kim, Hee-Jin;Cheong, Jae-Hoon;Ryu, Jong-Hoon;Ko, Kwang-Ho;Shin, Chan-Young
    • Biomolecules & Therapeutics
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    • 제18권1호
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    • pp.39-47
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    • 2010
  • Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

Positive Effects of Adiponectin, BDNF, and GLP-1 on Cortical Neurons Counteracting Palmitic Acid Induced Neurotoxicity

  • Danbi Jo;Seo Yeon Ahn;Seo Yoon Choi;Yoonjoo Choi;Dong Hoon Lee;Juhyun Song
    • Clinical Nutrition Research
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    • 제13권2호
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    • pp.121-129
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    • 2024
  • The prevalence of metabolic syndrome caused by diets containing excessive fatty acids is increasing worldwide. Patients with metabolic syndrome exhibit abnormal lipid profiles, chronic inflammation, increased levels of saturated fatty acids, impaired insulin sensitivity, excessive fat accumulation, and neuropathological issues such as memory deficits. In particular, palmitic acid (PA) in saturated fatty acids aggravates inflammation, insulin resistance, impaired glucose tolerance, and synaptic failure. Recently, adiponectin, brain-derived neurotrophic factor (BDNF), and glucose-like peptide-1 (GLP-1) have been investigated to find therapeutic solutions for metabolic syndrome, with findings suggesting that they are involved in insulin sensitivity, enhanced lipid profiles, increased neuronal survival, and improved synaptic plasticity. We investigated the effects of adiponectin, BDNF, and GLP-1 on neurite outgrowth, length, and complexity in PA-treated primary cortical neurons using Sholl analysis. Our findings demonstrate the therapeutic potential of adiponectin, BDNF, and GLP-1 in enhancing synaptic plasticity within brains affected by metabolic imbalance. We underscore the need for additional research into the mechanisms by which adiponectin, BDNF, and GLP-1 influence neural complexity in brains with metabolic imbalances.

Effects of Bee Venom and Sweet Bee Venom Acupuncture on Functional Recovery and c-Fos Expression in the Brain after Sciatic Crushed Nerve Injury in Rats

  • Choi, Seung-Peom;Song, Yun-Kyung;Lim, Hyung-Ho
    • 대한한의학회지
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    • 제31권3호
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    • pp.79-97
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    • 2010
  • Background: Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficit. Bee venom acupuncture has traditionally been used to treat several inflammatory diseases and chronic pain conditions. Objectives: The aims of this study were to compare the effects of bee venom (general bee venom, BV) and sweet bee venom (allergen-removed bee venom, SBV) acupuncture on the recovery rate of locomotor function, the expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve, and the expression of c-Fos in the brain following sciatic crushed nerve injury in rats, and to evaluate differences due to administration areas. Method: Walking track analysis, Western blot for BDNF and tyrosine receptor kinase B (TrkB), and immunohistochemistry for c-Fos were performed. In this study, comparative analyses of the effects of BV and SBV acupuncture in relation to administration sites, contralateral side or ipsilateral side, were conducted. Results: In the present result, sciatic function index (SFI) in walking track analysis significantly decreased following sciatic crushed nerve injury. The expressions of BDNF and TrkB in the sciatic nerve increased after induction of sciatic crushed nerve injury. C-Fos expression in the ventrolateral periaqueductal gray (vlPAG) and paraventricular nucleus (PVN) also increased. BV and SBV acupuncture treatment improved the SFI in walking track analysis. Treatment with SBV at 1mg/kg showed more potent enhancing effect on SFI compared to BV. Treatment with 1mg/kg BV or 1mg/kg SBV acupuncture suppressed the BDNF and TrkB expression in the sciatic nerve. BV and SBV acupuncture treatment also suppressed c-Fos expression in the PVN and vlPAG regions. Treatment with SBV at 1mg/kg showed more potent suppressing effect on c-Fos expression compared to BV when injected into the contralateral side of the injured nerve. Generally we could not find significant difference in the effects between contralateral side and ipsilateral side of the injured nerve. Conclusion: We have shown that BV and SBV acupuncture treatment can be used as the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.