• Title, Summary, Keyword: Neurotropic Factor

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APEX-1 Regulates Cell Proliferation through GDNF/GFRα1 Signaling (APEX-1은 GDNF/GFRα1 시그널을 통해 세포증식을 조절한다)

  • Kim, Hong-Beum;Hariharasudhan, Gurusamy;Youn, Cha-Kyung
    • Journal of Life Science
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    • v.23 no.10
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    • pp.1183-1191
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    • 2013
  • Human apurinic/apyrimidinic endonuclease (APEX-1) is a multifunctional protein that is capable of repairing abasic sites and single-strand breaks in damaged DNA. In addition, it serves as a redox-modifying factor for a number of transcription factors. Identifying the transcriptional targets of APEX-1 is essential for understanding how it affects various cellular outcomes. Expression array analysis was used to identify glial cell-derived neurotropic factor receptor ${\alpha}1$ ($GFR{\alpha}1$), which is an encoding receptor for the glial cell-derived neurotropic factor (GDNF) family, the expression of which is induced by APEX-1. A target of GDNF/$GFR{\alpha}$ signaling, c-Src (Tyr418) was strongly phosphorylated by GNDF in the APEX-1 expressing cells. Moreover, GDNF initiated cell proliferation, measured by counting the number of cells, in the APEX-1 expressing cells. Importantly, the down-regulation of APEX-1 by siRNA caused a marked reduction in the $GFR{\alpha}1$ expression level, and it reduced the ability of GDNF to phosphorylate c-Src (Tyr418) and stimulate cell proliferation. These results demonstrate an association between APEX-1 and GDNF/$GFR{\alpha}$ signaling and suggest a potential molecular mechanism for the involvement of APEX-1 in cell survival and proliferation.

Association between the Brain-Derived Neurotropic Factor and Attention Deficit Hyperactivity Disorder (BDNF가 ADHD의 병인과 치료에 미치는 영향)

  • Kang, Na Ri;Song, Jae Min;Kwack, Young-Sook
    • Korean Journal of Biological Psychiatry
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    • v.25 no.2
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    • pp.21-30
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    • 2018
  • Attention deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder. Recently, it has been suggested that brain-derived neurotropic factor (BDNF) may play a role in the pathogenesis of ADHD. Our aim of this review is to understand the physiological functions of BDNF and its potential relationship with ADHD and therapeutic approaches of ADHD. Searches were conducted in Pubmed and Research Information Service System (RISS). In this review, we summarized important literatures for the physiological functions of BDNF in neurodevelopment, change of serum BDNF level in ADHD, association of BDNF polymorphism and ADHD and potential association of treatment of ADHD with serum BDNF level. Further studies are required to more clearly understand the source and the role of BDNF in ADHD and to develop BDNF based-ADHD treatement.

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Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice

  • Weon, Jin Bae;Jung, Youn Sik;Ma, Choong Je
    • Biomolecules & Therapeutics
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    • v.24 no.3
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    • pp.298-304
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    • 2016
  • Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.

Effects of Memory and Learning Training on Neurotropic Factor in the Hippocampus after Brain Injury in Rats (뇌손상 흰쥐에서 기억과 학습훈련이 해마의 신경 성장인자에 미치는 영향)

  • Heo, Myoung;Bang, Yoo-Soon
    • The Journal of the Korea Contents Association
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    • v.9 no.2
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    • pp.309-317
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    • 2009
  • This study was to investigate the effects of restoring cognition function and neurotrophic factor in the hippocampus according to memory and learning training in rats affected by brain injury. Brain injury was induced in Sprague-Dawley rats(36 rats) through middle cerebral artery occlusion(MCAo). And then experiment groups were randomly divided into three groups; Group I: Brain injury induction(n=12), Group II: the application for treadmill training after brain injury induction(n=12), Group III: the application for memory and learning training after brain injury induction(n=12). Morris water maze acquisition test and retention test were performed to test cognitive function. And the histological examination was also observed through the immunohistochemistric response of BDNF(brain-derived neurotrophic factor) in the hippocampus. For Morris water maze acquisition test, there were significant interactions among the groups with the time(p<.001). The time to find the circular platform in Group III was more shortened than in Group I, II on the 9th, 10th, 11th and 12th day. For Morris water maze retention test, there were significant differences among the groups(p<.001). The time to dwell on quadrant circular platform in Group III on the 13th day was the longest compared with other groups. And as the result of observing the immunohistochemistric response of BDNF in the hippocampus CA1, the response of immunoreactive positive in Group III on the 7th day increased more than that of Group I, II. These results suggested that the memory and learning training in rats with brain injury has a more significant impact on restoring cognitive function via the changes of neurotropic factor expression and synaptic neuroplasticity.

Erythropoietin increases neuronal cell differentiation : association of transcriptional factors AP-l and NF-$\kappa$B activation

  • Lee, Sang-Min;Park, Hye-Ji;Lee, Yoot-Mo;Moon, Dong-Cheul;Kim, Kyong-Soon;Cho, Kyong-Ju;Yoon, Do-Young;Song, Suk-Gil;Hong, Jin-Tae
    • Proceedings of the PSK Conference
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    • pp.169.3-169
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    • 2003
  • Erythropietin (EPO), a hematopoietic factor is also required for normal brain development, and its receptor is localized in brain. Therefore, it is possible that EPO could act as a neurotropic factor inducing differentiation of neurons. The present study, we therefore investigated whether EPO can increase differentiation of undifferentiated cortical neuron isolated from postneonatal (Day 1) rat brains and PC12 cell, undifferentiated dopaminagic cell line. EPO dose (1-100 U/ml) dependently increased cell differentiation and expression of differentiation marker gene (neurofilament and tyrosine hydroxylase) in both cells. (omitted)

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Ape1/Ref-1 Stimulates GDNF/GFR ${\alpha}$ 1-mediated Downstream Signaling and Neuroblastoma Proliferation

  • Kang, Mi-Young;Kim, Kweon-Young;Yoon, Young;Kang, Yoon-Sung;Kim, Hong-Beum;Youn, Cha-Kyung;Kim, Dong-Hui;Kim, Mi-Hwa
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.5
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    • pp.349-356
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    • 2009
  • We previously reported that glial cell line-derived neurotropic factor (GDNF) receptor ${\alpha}$ 1 (GFR ${\alpha}$ 1) is a direct target of apurinic/apyrimidinic endonuclease 1 (Ape1/Ref-1). In the present study, we further analyzed the physiological roles of Ape1/Ref-1-induced GFR ${\alpha}$ 1 expression in Neuro2a mouse neuroblastoma cells. Ape1/Ref-1 expression caused the clustering of GFR ${\alpha}$ 1 immunoreactivity in lipid rafts in response to GDNF. We also found that Ret, a downstream target of GFR ${\alpha}$ 1, was functionally activated by GDNF in Ape1/Ref-1-expressing cells. Moreover, GDNF promoted the proliferation of Ape1/Ref-1-expressing Neuro2a cells. Furthermore, GFR ${\alpha}$ 1-specific RNA experiments demonstrated that the downregulation of GFR ${\alpha}$ 1 by siRNA in Ape1/Ref-1-expressing cells impaired the ability of GDNF to phosphorylate Akt and PLC ${\gamma}$-1 and to stimulate cellular proliferation. These results show an association between Ape1/Ref-1 and GDNF/GFR ${\alpha}$ signaling, and suggest a potential molecular mechanism for the involvement of Ape1/Ref-1 in neuronal proliferation.

Neuroprotective effects of Sohaphwangwon essential oil in a Parkinson's disease mouse model (MPTP로 유도된 Parkinson's disease 동물 모델을 이용한 소합향원(蘇合香元)의 신경보호 효과 및 그 작용 기전 연구)

  • Kim, In-Ja;Lee, Ji-Hyun;Song, Kyoo-Ju;Koo, Byung-Soo;Kim, Geun-Woo
    • Journal of Oriental Neuropsychiatry
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    • v.23 no.1
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    • pp.129-143
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    • 2012
  • Objectives : To evaluate the neuroprotective effects of the essential oil from Sohaphwangwon (SH), a Chinese traditional medicinal prescription in a Parkinson's disease mouse model. Methods : 1. The neuroprotective effect of SH on primary neuronal cells was examined by using 1-methyl-4-phenylpyridinium ion (MPP+). 2. The neuroprotective effect of SH was examined in a Parkinson's disease mouse model. C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day), intraperitoneal (i.p.) for 5 days. SH inhalation was applied before MPTP treatment for 7 days and continued until 12 days after the first MPTP treatment. 3. To find out the intracellular target signal molecule(s) regarding the neuroprotective effect of SH essential oil, brain-derived neurotropic factor (BDNF) and synaptic protein SNAP25 were examined by Western blot analysis. Results : 1. MPP+ induced a concentration-dependent decrease in cell viability. However, in the presence of 3 and 5 ug/ml of SH, MPP+-induced cell death was significantly reduced. 2. SH inhalation in MPTP mice led to the restoration of behavioral impairment and rescued tyrosine hydroxylase (TH)-positive dopaminergic neurodegeneration. 3. In SH / MPTP mice, BDNF and SNAP25 increased. Conclusions : This experiment suggests that the neuroprotective effect of SH essential oil is mediated by the expression of BDNF. Furthermore, SH essential oil may serve as a potential preventive or therapeutic agent regarding Parkinson's disease.

The Effect of Exercise Training on Aβ-42, BDNF, GLUT-1 and HSP-70 Proteins in a NSE/ APPsw-transgenic Model for Alzheimer's Disease. (지구성 운동이 NSE/APPsw 알츠하이머 질환 생쥐의 인지능력, Aβ-42, BDNF, GLUT-1과 HSP-70 단백질 발현에 미치는 영향)

  • Eum, Hyun-Sub;Kang, Eun-Bum;Lim, Yea-Hyun;Lee, Jong-Rok;Cho, In-Ho;Kim, Young-Soo;Chae, Kab-Ryoung;Hwang, Dae-Yean;Kwak, Yi-Sub;Oh, Yoo-Sung;Cho, Joon-Yong
    • Journal of Life Science
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    • v.18 no.6
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    • pp.796-803
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    • 2008
  • Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.