• Title/Summary/Keyword: neurotrophic factor

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Epigenetic Mechanisms of Depression: Role of Histone Modification and DNA Methylation in BDNF Gene (우울증의 후성유전기전: BDNF 유전자의 히스톤 변형 및 DNA 메틸화의 역할)

  • Park, Sung Woo
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1536-1544
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    • 2018
  • Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.

Paracrine influence of human perivascular cells on the proliferation of adenocarcinoma alveolar epithelial cells

  • Kim, Eunbi;Na, Sunghun;An, Borim;Yang, Se-Ran;Kim, Woo Jin;Ha, Kwon-Soo;Han, Eun-Taek;Park, Won Sun;Lee, Chang-Min;Lee, Ji Yoon;Lee, Seung-Joon;Hong, Seok-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.2
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    • pp.161-168
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    • 2017
  • Understanding the crosstalk mechanisms between perivascular cells (PVCs) and cancer cells might be beneficial in preventing cancer development and metastasis. In this study, we investigated the paracrine influence of PVCs derived from human umbilical cords on the proliferation of lung adenocarcinoma epithelial cells (A549) and erythroleukemia cells (TF-$1{\alpha}$ and K562) in vitro using $Transwell^{(R)}$ co-culture systems. PVCs promoted the proliferation of A549 cells without inducing morphological changes, but had no effect on the proliferation of TF-$1{\alpha}$ and K562 cells. To identify the factors secreted from PVCs, conditioned media harvested from PVC cultures were analyzed by antibody arrays. We identified a set of cytokines, including persephin (PSPN), a neurotrophic factor, and a key regulator of oral squamous cell carcinoma progression. Supplementation with PSPN significantly increased the proliferation of A549 cells. These results suggested that PVCs produced a differential effect on the proliferation of cancer cells in a cell-type dependent manner. Further, secretome analyses of PVCs and the elucidation of the molecular mechanisms could facilitate the discovery of therapeutic target(s) for lung cancer.

Isolation and Identification of Prepubertal Buffalo (Bubalus bubalis) Spermatogonial Stem Cells

  • Feng, Wanyou;Chen, Shibei;Do, Dagiang;Liu, Qinyou;Deng, Yanfei;Lei, Xiaocan;Luo, Chan;Huang, Ben;Shi, Deshun
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.10
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    • pp.1407-1415
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    • 2016
  • Isolation and culture of spermatogonial stem cells (SSCs) are attractive for production of genetic modified offspring. In the present study, buffalo spermatogonial stem-like cells were isolated, cultured and expression pattern of different germ cell marker genes were determined. To recover spermatogonia, testes from age 3 to 7 months of buffalo were decapsulated, and seminiferous tubules were enzymatically dissociated. Two types of cells, immature sertoli cell and type A spermatogonia were observed in buffalo testes in this stage. Germ cell marker genes, OCT3/4 (Pou5f1), THY-1, c-kit, PGP9.5 (UCHL-1) and Dolichos biflorus agglutinin, were determined to be expressed both in mRNA and protein level by reverse transcription polymerase chain reaction and immunostaining in buffalo testes and buffalo spermatogonial stem-like cells, respectively. In the following, when the isolated buffalo buffalo spermatogonial stem-like cells were cultured in the medium supplemented 2.5% fetal bovine serum and 40 ng/mL glial cell-derived neurotrophic factor medium, SSCs proliferation efficiency and colony number were significantly improved than those of other groups (p<0.05). These findings may help in isolation and establishing long term in vitro culture system for buffalo spermatogonial stem-like cells, and accelerating the generation of genetic modified buffaloes.

The New Neurobiology of Depression (우울증의 새로운 신경생물학)

  • Kim, Yong Ku
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.3-19
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    • 2001
  • Recent basic and clinical studies demonstrate a major role for neural plasticity in the etiology and treatment of depression and stress-related illness. The neural plasticity is reflected both in the birth of new cell in the adult brain(neurogenesis) and the death of genetically healthy cells(apoptosis) in the response to the individual's interaction with the environment. The neural plasticity includes adaptations of intracellular signal transduction pathway and gene expression, as well as alterations in neuronal morphology and cell survival. At the cellular level, repeated stress causes shortening and debranching of dendrite in the CA3 region of hippocampus and suppress neurogenesis of dentate gyrus granule neurons. At the molecular level, both form of structural remodeling appear to be mediated by glucocorticoid hormone working in concert with glutamate and N-methyl-D-aspartate(NMDA) receptor, along with transmitters such as serotonin and GABA-benzodiazepine system. In addition, the decreased expression and reduced level of brain-derived neurotrophic factor(BDNF) could contribute the atrophy and decreased function of stress-vulnerable hippocampal neurons. It is also suggested that atrophy and death of neurons in the hippocampus, as well as prefrontal cortex and possibly other regions, could contribute to the pathophysiology of depression. Antidepressant treatment could oppose these adverse cellular effects, which may be regarded as a loss of neural plasticity, by blocking or reversing the atrophy of hippocampal neurons and by increasing cell survival and function via up-regulation of cyclic adenosine monophosphate response element-binding proteins(CREB) and BDNF. In this article, the molecular and cellular mechanisms that underlie stress, depression, and action of antidepressant are precisely discussed.

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Convergence Study on the Effects of Using Convergence Aerobic Exercise on the Brain-derived neurotrophic factor and Blood Lipids in Elderly Women with Mild Dementia (유산소 운동이 경증치매 여성노인의 BDNF 및 혈중지질에 미치는 효과에 관한 융합 연구)

  • Nam, Sang-Nam;Lim, Youn-Sub
    • Journal of the Korea Convergence Society
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    • v.8 no.8
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    • pp.345-353
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    • 2017
  • This study attempts to explore changes in the BDNF and blood lipid level through a 12-week aerobic exercise program aimed at the elderly women of a misdemeanor dementia, and was carried out for 3 times a week, 50 minutes each with the exercise angle 9-14. The following conclusions were obtained through this purpose and procedure. First, the results of BDNF showed a significant increase in the exercise group after conducting a 12-week aerobic exercise program. Second, after a 12-week aerobic exercise program in the athletic group, the results of the blood stop has showed the reduction of both total cholesterol and low density lipoprotein cholesterol, and the amount of high density lipoprotein cholesterol has increased. Therefore, the aerobic exercise program conducted in this study has a positive effect on lipid improvement along with dementia prevention, and through it helps to improve the quality of life of the elderly including significant improvement in physical and mental health.

Probiotic Mixture KF Attenuates Age-Dependent Memory Deficit and Lipidemia in Fischer 344 Rats

  • Jeong, Jin-Ju;Kim, Kyung-Ah;Ahn, Young-Tae;Sim, Jae-Hun;Woo, Jae-Yeon;Huh, Chul-Sung;Kim, Dong-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.25 no.9
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    • pp.1532-1536
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    • 2015
  • To investigate the memory-enhancing effect of lactic acid bacteria, we selected the probiotic mixture KF, which consisted of Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 (1 × 1011 CFU/g of each strain), and investigated its antilipidemic and memoryenhancing effects in aged Fischer 344 rats. KF (1 × 1010 CFU/rat/day), which was administered orally once a day (6 days per week) for 8 weeks, significantly inhibited age-dependent increases of blood triglyceride and reductions of HDL cholesterol (p < 0.05). KF restored agereduced spontaneous alternation in the Y-maze task to 94.4% of that seen in young rats (p < 0.05). KF treatment slightly, but not significantly, shortened the escape latency daily for 4 days. Oral administration of KF restored age-suppressed doublecortin and brain-derived neurotrophic factor expression in aged rats. Orally administered KF suppressed the expression of p16, p53, and cyclooxygenase-2, the phosphorylation of Akt and mTOR, and the activation of NF-κB in the hippocampus of the brain. These findings suggest that KF may ameliorate age-dependent memory deficit and lipidemia by inhibiting NF-κB activation.

Alteration in Plasma BDNF Level after Repetitive Transcranial Magnetic Stimulation(rTMS) in Treatment-Resistant Schizophrenia : A Pilot Study (치료저항성 정신분열병 환자에서 반복적 경두개자기자극술 병행치료시 혈장 BDNF 농도 변화 : 예비 연구)

  • Oh, So-Young;Kim, Yong-Ku
    • Korean Journal of Biological Psychiatry
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    • v.16 no.3
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    • pp.170-180
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    • 2009
  • Objectives : To assess clinical improvement and change in plasma brain-derived neurotrophic factor(BDNF) level after repetitive transcranial magnetic stimulation(rTMS) in patients with treatment-resistant schizophrenia. Methods : Seven patients with DSM-IV schizophrenia, who were proven to be treatment-resistant, were treated with 15 sessions of rTMS for three weeks as an adjuvant therapy to antipsychotic treatment. Clinical improvement and change in plasma BDNF level were measured after the treatment period. The symptom severity was assessed with the Positive and Negative Syndrome Scale(PANSS) and the Korean Version of Calgary Depression Scale for Schizophrenia(K-CDSS) at baseline and 7 days after the treatment. Plasma BDNF level was measured by enzyme-linked immunosorbent assay(ELISA) at baseline and 7 days after the treatment. Results : After the rTMS treatment, there was no significant improvement in PANSS total score(Z=-1.693, p=0.090) and no significant change in plasma BDNF was found(Z=-1.183, p=0.237). Negative correlations were found between percentage change in PANSS positive subscale score and duration of illness(rho=-0.991, N=7, p<0.0005, two-tailed), and PANSS negative subscale score at baseline and percentage change in plasma BDNF level(rho=-0.821, N=7, p=0.023, two-tailed). Conclusion : This preliminary study suggests that rTMS didn't make a significant change in clinical symptoms nor in plasma BDNF level in treatment-resistant schizophrenia. Percentage change in plasma BDNF, however, might be correlated with treatment resistance in schizophrenic patients. This is a pilot study with a small sample size, therefore, a further study with a larger sample size is needed.

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Effects of Gastrodiae Elata Pharmacopuncture at GB20 on Motor Control and Cognitive Function in Mild TBI Rats (중등도 외상성 뇌손상 흰쥐에서 천마약침(天麻藥鍼)이 운동조정 및 인지 기능회복에 미치는 효과)

  • Kim, Kyung-Yoon;Jeong, Hyun-Woo;Kim, Gye-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.5
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    • pp.1080-1086
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    • 2009
  • This study was designed to investigate the effects of Gastrodiae Elata Pharmacopuncure at GB20 on motor control and cognitive dysfunction recovery after mild traumatic brain injury in rats. Rats were divided into three groups; (1) no treatment after traumatic brain injury(experiment I), (2) Treatment with NPA after traumatic brain injury(experiment II), (3) Treatment with GEP after traumatic brain injury(experiment III). In our study, we carried out behavioral test(Rotarod, Morris water maze) and immunohistochemistry study of the change BDNF in the hippocampus(pre, $7^{th}$, $14^{th}$ day). In Rotarod test(motor control function) was significantly increased in the experimental group III as compared with experimental group I, II on $7^{th}$(p<0.01) and $14^{th}$ day(p<0.001). In Morris water maze test(cognitive function) was significantly decreased in the experimental group III as compared with experimental group I, II on $14^{th}$ day(p<0.001). In immunohistochemistric response of BDNF in the hippocampus, the experimental group III was more immune response than the other groups on $14^{th}$ day. These results imply that Gastrodiae Elata Pharmacopuncure at GB20 can play a role in facilitating recovery of motor control and cognitive function after mild traumatic brain injury in rats.

Effects of Treadmill Exercise on Memory, Hippocampal Cell Proliferation, BDNF, TrkB, and Forebrain Cholinergic Cells in Adolescent Rats (트레드밀 운동이 청소년기 흰쥐의 기억력과 해마 신경세포생성, BDNF, TrkB, 그리고 전뇌 콜린 세포에 미치는 영향)

  • Lee, Hee-Hyuk
    • Journal of Life Science
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    • v.19 no.3
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    • pp.403-410
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    • 2009
  • This study investigated the effects of treadmill exercise on memory ability, cell proliferation, BDNF, and TrkB in the hippocampus and forebrain cholinergic cells in adolescent rats. Male Sprague-Dawley rats (4 weeks old) were randomly assigned to the following two groups: the sedentary group (n=10) and the exercise group (n=10). Rats in the exercise group were forced to run on a treadmill for 30 min, five times per week for 4 weeks. The latency of the step-through avoidance task was used in order to evaluate memory ability. Hippocampal brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB) expression were assessed by Western blotting. Hippocampal cell proliferation and forebrain cholinergic cells were assessed by immunohistochemistry. The present study showed that treadmill running during the adolescent period significantly improved memory capability, increased hippocampal cell proliferation, up-regulated hippocampal BDNF and TrkB expression, and enhanced the number of forebrain cholinergic cells. These results suggest that regular exercise during the adolescent period may enhance memory function.

Antidepressant effect of water extract of Taraxacum platycarpum through BDNF, ERK and CREB pathway (BDNF, ERK 및 CREB 경로를 통한 포공영 추출물의 항우울 효과)

  • Gu, Pil Sung;Lee, Jihye;Choi, Yun Hee;Jung, Ji Wook
    • The Korea Journal of Herbology
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    • v.30 no.3
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    • pp.13-17
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    • 2015
  • Objectives : Taraxacum platycarpum H. Dahlstedt has been reported to have several biological properties such as skin hydration and antiinflammation. The purpose of this study was to examine the antidepressive effects of water extract of T. platycarpum (WTP) on an animal model of depression. Methods : In the present study, normal ICR mice (4 weeks) were used, and orally administered with WTP (25, 50 and 100 mg/kg). Depression-like behavior was monitored the forced swimming test (FST) and tail suspension test (TST) in mice. The locomotor activity was evaluated to eliminate the false-positive activity in the open field test (OFT). Fluoxetine, the selective serotonin reuptake inhibitor, as a positive control was intraperitoneally administered at a dose of 15 mg/kg at 30 min before starting the behavioral test. Moreover, we evaluated the effects of WTP on the expression of brain-derived neurotrophic factor (BDNF) and the extracellular signal-regulated kinase (ERK)/ cyclic AMP response-element binding protein (CREB) signaling pathway in the hippocampus using Western blot. Results : The administration of WTP (50 and 100 mg/kg) significantly (P < 0.05, respectively) reduced the immobility time during FST and TST without accompanying changes in locomotor activity by OFT. Furthermore, WTP at dose of 100 mg/kg increased the BDNF expression and the phosphorylation of ERK and CREB in the hippocampus region. Conclusions : These results suggest that WTP has a useful anti-depressant effect through the regulation of BDNF/ERK/CREB signaling pathway.