• 제목/요약/키워드: neurotrophic factor

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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.

Exploring the role and mechanisms of diallyl trisulfide and diallyl disulfide in chronic constriction-induced neuropathic pain in rats

  • Wang, Gang;Yang, Yan;Wang, Chunfeng;Huang, Jianzhong;Wang, Xiao;Liu, Ying;Wang, Hao
    • The Korean Journal of Pain
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    • 제33권3호
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    • pp.216-225
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    • 2020
  • Background: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of H2S, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall-Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery. Results: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of H2S, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Co-administration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating H2S levels. Conclusions: Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of H2S-BDNF-Nrf2 signaling pathway.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

  • Karaoz, Erdal;Tepekoy, Filiz;Yilmaz, Irem;Subasi, Cansu;Kabatas, Serdar
    • Journal of Korean Neurosurgical Society
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    • 제62권2호
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    • pp.153-165
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    • 2019
  • Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

Effect of Single Growth Factor and Growth Factor Combinations on Differentiation of Neural Stem Cells

  • Choi, Kyung-Chul;Yoo, Do-Sung;Cho, Kyung-Sock;Huh, Pil-Woo;Kim, Dal-Soo;Park, Chun-Kun
    • Journal of Korean Neurosurgical Society
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    • 제44권6호
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    • pp.375-381
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    • 2008
  • Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

해인탕 추출물이 흰쥐 좌골신경 손상 모델에서 기능회복과 뇌의 c-Fos 발현에 미치는 영향 (Effects of Haein-tang(Hairen-tang) Extract on Functional Recovery in Sciatic Nerve and c-Fos Expression in the Brain after Crushed Sciatic Nerve Injury in Rats)

  • 은영준;송윤경;임형호
    • 한방재활의학과학회지
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    • 제21권2호
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    • pp.125-142
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    • 2011
  • Objectives : Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficits. The purpose of this study was to evaluate the effects of Haein-tang(Hairen-tang) extract on functional recovery and pain release in the sciatic nerve after crushed sciatic nerve injury in rats. Methods : 1. Sciatic functional index(SFI) were performed on functional recovery. 2. c-Fos immunohistochemistry were performed on c-Fos expressions in the paraventricular nucleus(PVN) and ventrolateral periaqueductal gray(vIPAG). 3. Neurofilament immunohistochemistry were performed on neurofilament regeneration. 4. Western blot were performed on brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) expression. Results : 1. Haein-tang(Hairen-tang) extract significantly enhanced the SFI value in the sciatic nerve injury and 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. 2. Haein-tang(Hairen-tang) extract significantly suppressed the sciatic nerve injury-induced increment of c-Fos expressions in the PVN and vIPAG in the sciatic nerve injury and 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. 3. Haein-tang(Hairen-tang) extract significantly increased neurofilament expression in the sciatic nerve injury and 50 mg/kg, 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. 4. Haein-tang(Hairen-tang) extract significantly controled the sciatic nerve injury-induced increment of BDNF and NGF expressions in the sciatic nerve injury and 100 mg/kg, 200 mg/kg Haein-tang(Hairen-tang)-treated group. Conclusions : These results suggest that Haein-tang(Hairen-tang) treatment after sciatic nerve injury is effective for the functional recovery by enhancing of axonal regeneration and suppressing of pain.

12주 복합운동이 비만 여고생의 뇌신경세포 생성인자 및 염증인자에 미치는 영향 (The Effects of 12 Weeks Combined Exercise on Brain Nerve Growth Factor, Inflammation-Related Factor in Obese High School Girls)

  • 서정표;허준회;김현준;박장준
    • 대한통합의학회지
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    • 제8권1호
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    • pp.159-168
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    • 2020
  • Purpose : To provide data on exercise prescription for obesity management and prevention of cardiovascular disease in girl's high school and to prepare basic data for more effective exercise program for lifestyle improvement and prevention of lifestyle-related diseases. This study examines the effects on brain nerve growth factor and inflammatory factors, and the relationship between obesity factor and brain neuron cell production factor and inflammatory factor changes by complex exercise. Methods : The subjects of the study were obese students with a body fat percentage of 30 % or higher after obtaining body fat percentage of high school girls in C-city. Among them, 20 students who wanted to participate in the program of this study and did not participate in special exercise and diet therapy within the last 6 months were radio-sampled into groups of exercise group and control group, but attendance rate was low and The final exercise group (9) and control group (9) were measured, except for one student who did not respond. Results : Analysis of the range of variation in body composition, BMI, lean body mass, and the interaction between the groups showed significant differences (p<.05). TC, TG, HDL-C, and LDL-C as variables of blood lipids, TC and TG were not significantly different and TG was significantly different (p<.05) in interactions. HDL-C showed a significant difference (p<.01) in interactions, an increase in exercise group, and a significant decrease in control group (p<.05). There was a significant difference (p<.05) in BDNF interaction, an increase in the exercise group and a decrease in the control group, but no significant difference. NGF tended to increase in both exercise and control groups. IL-6 had a significant difference in timing (p<.05) and significantly decreased (p<.01) in the exercise group, and TNF-α interacted with timing (p<.05), and a significant increase in the control group. Conclusion : This study confirmed 12-week compound exercise program was effective in increasing the expression of basal fitness or CNS factor, but not enough to actually improve brain function. Fat mass and obesity are also affecting vascular inflammatory factors.

생쥐 신경교세포 유래 신경영양인자 유도성 전사인자 (mGIF) 유전자의 유전체 구조 및 프로모터 특성 분석 (Genomic Organization and Promoter Characterization of the Murine Glial Cell-derived Neurotrophic Factor Inducible Transcription Factor (mGIF) Gene)

  • 김옥수;김용만;김남영;이어진;장민경;이동근;이상현
    • 생명과학회지
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    • 제17권2호통권82호
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    • pp.167-173
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    • 2007
  • 생쥐 신경교세포 유래 신경영양인자 유도성 전사인자(mGIF)의 발현조절에 필요한 전사기작을 연구하기 위하여 mGIF cDNA를 탐침자로 이용하여 genomic clone을 분리하였다. 전체 유전자 13-kb 영역 중 전사개시점에서 4-kb 상류영역의 유전자 서열을 파악한 결과, 프로모터 영역에서 TATA box와 CAAT box는 발견할 수 없었으며 G+C content는 높은 것으로 나타났고 여러 개의 Sp1 전사인자 결합영역이 있었다. 또한 mGIF 유전자는 AP2 결합에 필요한 보존적 영역이 있었다. mGIF 유전자의 프로모터 영역의 단편들을 프로모터가 없는 pGL2-Basic 플라스미드의 luciferase 유전자의 상류에 연결하여 서로 다른 5종류의 결손 돌연변이체를 제조하고 NB41A3 세포주를 이용하여 전사활성을 측정하였다. Transient expression assays 결과, 모든 결손 돌연변이체에서 전사활성이 나타났으며 -213과 -129사이에 전사촉진 영역이 존재하며 -806과 -214사이에 전사억제 영역이 있는 것으로 나타났다. 신경세포주인 NB41A3과 신경교세포주인 C6 그리고 간세포주인 HepG2에서 mGIF 유전자 프로모터의 높은 활성이 관찰되었으며, 근육세포주인 C2C12에서는 낮은 활성이 관찰되었다. 따라서 mGIF 유전자는 조직특이적으로 발현하며 도파민 수용체 유전자와 구조적, 기능적 유사성이 있는 것을 알 수 있었다.

Panax ginseng exerts antidepressant-like effects by suppressing neuroinflammatory response and upregulating nuclear factor erythroid 2 related factor 2 signaling in the amygdala

  • Choi, Jong Hee;Lee, Min Jung;Jang, Minhee;Kim, Hak-Jae;Lee, Sanghyun;Lee, Sang Won;Kim, Young Ock;Cho, Ik-Hyun
    • Journal of Ginseng Research
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    • 제42권1호
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    • pp.107-115
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    • 2018
  • Background: Depression is one of the most commonly diagnosed neuropsychiatric diseases, but the underlying mechanism and medicine are not well-known. Although Panax ginseng has been reported to exert protective effects in various neurological studies, little information is available regarding its antidepressant effects. Methods: Here, we examined the antidepressant effect and underlying mechanism of P. ginseng extract (PGE) in a chronic restraint stress (CRS)-induced depression model in mice. Results: Oral administration of PGE for 14 d decreased immobility (depression-like behaviors) time in forced swim and tail suspended tests after CRS induction, which corresponded with attenuation of the levels of serum adrenocorticotropic hormone and corticosterone, as well as attenuated c-Fos expression in the amygdala. PGE enhanced messenger RNA expression level of brain-derived neurotrophic factor but ameliorated microglial activation and neuroinflammation (the level of messenger RNA and protein expression of cyclooxygenase-2 and inducible nitric oxide synthase) in the amygdala of mice after CRS induction. Interestingly, 14-d treatment with celecoxib, a selective cyclooxygenase-2 inhibitor, and $N_{\omega}$-nitro-L-arginine methyl ester hydrochloride, a selective inducible nitric oxide synthase inhibitor, attenuated depression-like behaviors after CRS induction. Additionally, PGE inhibited the upregulation of the nuclear factor erythroid 2 related factor 2 and heme oxygenase-1 pathways. Conclusion: Taken together, our findings suggest that PGE exerts antidepressant-like effect of CRS-induced depression by antineuroinflammatory and antioxidant (nuclear factor erythroid 2 related factor 2/heme oxygenase-1 activation) activities by inhibiting the hypothalamo-pituitary-adrenal axis mechanism. Further studies are needed to evaluate the potential of components of P. ginseng as an alternative treatment of depression, including clinical trial evaluation.

Protective Effects of Silibinin and Its Possible Mechanism of Action in Mice Exposed to Chronic Unpredictable Mild Stress

  • Yan, Wen-Jing;Tan, Ying-Chun;Xu, Ji-Cheng;Tang, Xian-Ping;Zhang, Chong;Zhang, Peng-Bo;Ren, Ze-Qiang
    • Biomolecules & Therapeutics
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    • 제23권3호
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    • pp.245-250
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    • 2015
  • Silibinin, a natural flavonoid antioxidant isolated from extracts of the milk thistle herb, has recently been identified as having anti-hepatotoxic and anticancer properties. In this paper, we investigated the effects of silibinin on behavior and neuroplasticity in mice subjected to chronic unpredictable mild stress (CUMS). After 5 consecutive weeks of CUMS, the mice were treated with silibinin (100 mg/kg, 200 mg/kg and 400 mg/kg by oral gavage) for 3 consecutive weeks. The results showed that silibinin administration significantly alleviated the CUMS-induced depressive-like behavior, including the total number of squares crossed and the frequency of rearing in the open field test, the immobility time in the tail suspension test and the forced swimming test. Furthermore, silibinin treatment increased the levels of brain-derived neurotrophic factor (BDNF), serotonin (5-HT) and norepinephrine (NE) in the prefrontal cortex and hippocampus. Our study provides new insight into the protective effects of silibinin on the depressive status of CUMS mice, specifically by improving neuroplasticity and neurotransmission.

Epac2 contributes to PACAP-induced astrocytic differentiation through calcium ion influx in neural precursor cells

  • Seo, Hyunhyo;Lee, Kyungmin
    • BMB Reports
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    • 제49권2호
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    • pp.128-133
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    • 2016
  • Astrocytes play a critical role in normal brain functions and maintaining the brain microenvironment, and defects in astrocytogenesis during neurodevelopment could give rise to severe mental illness and psychiatric disorders. During neuro-embryogenesis, astrocytogenesis involves astrocytic differentiation of neural precursor cells (NPCs) induced by signals from ciliary neurotrophic factor (CNTF) or pituitary adenylate cyclase-activating peptide (PACAP). However, in contrast to the CNTF signaling pathway, the exact mechanism underlying astrocytic differentiation induced by PACAP is unknown. In the present study, we aimed to verify a signaling pathway specific to PACAP-induced astrocytogenesis, using exchange protein directly activated by cAMP2 (Epac2)-knockout mice. We found that PACAP could trigger astrocytic differentiation of NPCs via Epac2 activation and an increase in the intracellular calcium concentration via a calcium ion influx. Taken together, we concluded that astrocytogenesis stimulated by PACAP occurs through a novel signaling pathway independent from CNTF-JAK/STAT signaling, that is the well-known pathway of astrocytogenesis.