• 제목/요약/키워드: Nerve growth factor

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A comprehensive review of the therapeutic effects of Hericium erinaceus in neurodegenerative disease

  • Kim, Young Ock;Lee, Sang Won;Kim, Jin Seong
    • 한국버섯학회지
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    • 제12권2호
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    • pp.77-81
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    • 2014
  • Mushrooms are considered not only as food but also for source of physiologically beneficial medicines. The culinary-medicinal mushrooms may important role in the prevention of age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. Hericium erinaceus (H. erinaceus), is edible mushrooms, is a parasitic fungus that grows hanging off of logs and trees and well established candidate for brain and nerve health. H. erinaceus contains high amounts of antioxidants, beta-glucan, polysaccharides and a potent catalyst for brain tissue regeneration and helps to improve memory and cognitive functions. Its fruiting bodies and the fungal mycelia exhibit various pharmacological activities, including the enhancement of the immune system, antitumor, hypoglycemic and anti-aging properties. H. erinaceus stimulates the synthesis of Nerve Growth Factor (NGF) which is the primary protein nutrient responsible for enhancing and repairing neurological disorders. Especially hericenones and erinacines isolated from its fruitin body stimulate NGF, synthesis. This fungus is also utilized to regulate blood levels of glucose, triglycerides and cholesterol. H. erinaceus can be considered as useful therapeutic agents in the management and/or treatment of neurodegeneration diseases. However, this review focuses on in vitro, in vivo and clinical trials for neurodegerative disease.

백서 설신경 압박손상모델에서 신경성장인자 유전자 주입이 신경재생에 미치는 영향 (EFFECT OF NERVE GROWTH FACTOR GENE INJECTION ON THE NERVE REGENERATION IN RAT LINGUAL NERVE CRUSH-INJURY MODEL)

  • 고은봉;정헌종;안강민;김성민;김윤희;장정원;이종호
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제28권5호
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    • pp.375-395
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    • 2006
  • Purpose: Lingual nerve (LN) damage may be caused by either tumor resection or injury such as wisdom tooth extraction, Although autologous nerve graft is sometimes used to repair the damaged nerve, it has the disadvantage of necessity of another operation for nerve harvesting. Moreover, the results of nerve grafting is not satisfactory. The nerve growth factor (NGF) is well-known to play a critical role in peripheral nerve regeneration and its local delivery to the injured nerve has been continuously tried to enhance nerve regeneration. However, its application has limitations like repeated administration due to short half life of 30 minutes and an in vivo delivery model must allow for direct and local delivery. The aim of this study was to construct a well-functioning $rhNGF-{\beta}$ adenovirus for the ultimate development of improved method to promote peripheral nerve regeneration with enhanced and extended secretion of hNGF from the injured nerve by injecting $rhNGF-{\beta}$ gene directly into crush-injured LN in rat model. Materials and Methods: $hNGF-{\beta}$ gene was prepared from fetal brain cDNA library and cloned into E1/E3 deleted adenoviral vector which contains green fluorescence protein (GFP) gene as a reporter. After large scale production and purification of $rhNGF-{\beta}$ adenovirus, transfection efficiency and its expression at various cells (primary cultured Schwann cells, HEK293 cells, Schwann cell lines, NIH3T3 and CRH cells) were evaluated by fluorescent microscopy, RT-PCR, ELISA, immunocytochemistry. Furthermore, the function of rhNGF-beta, which was secreted from various cells infected with $rhNGF-{\beta}$ adenovirus, was evaluated using neuritogenesis of PC-12 cells. For in vivo evaluation of efficacy of $rhNGF-{\beta}$ adenovirus, the LNs of 8-week old rats were exposed and crush-injured with a small hemostat for 10 seconds. After the injury, $rhNGF-{\beta}$ adenovirus($2{\mu}l,\;1.5{\times}10^{11}pfu$) or saline was administered into the crushed site in the experimental (n=24) and the control group (n=24), respectively. Sham operation of another group of rats (n=9) was performed without administration of either saline or adenovirus. The taste recovery and the change of fungiform papilla were studied at 1, 2, 3 and 4 weeks. Each of the 6 animals was tested with different solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) by two-bottle test paradigm and the number of papilla was counted using SEM picture of tongue dorsum. LN was explored at the same interval as taste study and evaluated electro-physiologically (peak voltage and nerve conduction velocity) and histomorphometrically (axon count, myelin thickness). Results: The recombinant adenovirus vector carrying $rhNGF-{\beta}$ was constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. GFP expression was observed in 90% of $rhNGF-{\beta}$ adenovirus infected cells compared with uninfected cells. Total mRNA isolated from $rhNGF-{\beta}$ adenovirus infected cells showed strong RT-PCR band, however uninfected or LacZ recombinant adenovirus infected cells did not. NGF quantification by ELISA showed a maximal release of $18865.4{\pm}310.9pg/ml$ NGF at the 4th day and stably continued till 14 days by $rhNGF-{\beta}$ adenovirus infected Schwann cells. PC-12 cells exposed to media with $rhNGF-{\beta}$ adenovirus infected Schwann cell revealed at the same level of neurite-extension as the commercial NGF did. $rhNGF-{\beta}$ adenovirus injected experimental groups in comparison to the control group exhibited different taste preference ratio. Salty, sweet and sour taste preference ratio were significantly different after 2 weeks from the beginning of the experiment, which were similar to the sham group, but not to the control group.

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice

  • Moon, Eunjung;Lee, Sung Ok;Kang, Tong Ho;Kim, Hye Ju;Choi, Sang Zin;Son, Mi-Won;Kim, Sun Yeou
    • Biomolecules & Therapeutics
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    • 제22권5호
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    • pp.445-452
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    • 2014
  • The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

향부자가 estradiol valerate로 유발된 백서의 다낭성 난소에 미치는 영향 (Effects of Cyperi Rhizoma(CR) on the Polycystic Ovaries Induced by Estradiol Valerate in Rats)

  • 양동선;양승정;조성희;박경미;김형우;조수인
    • 대한한방부인과학회지
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    • 제23권4호
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    • pp.35-46
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    • 2010
  • Purpose: This study was designed to investigate the effects of Cyperi Rhizoma (CR) on changes in weights morphological and histopathological observations in Polycystic Ovary(PCO) rats. Methods: PCO was induced by single intramuscular injection with EV(2mg) in female rats. Normal group(n=8) were injected with sesame oil and orally administrated distilled water for five weeks. PCO control group(n=8) were injected with EV and orally administrated distilled water for five weeks. CR treated group(n=8) were injected with EV and orally administrated CR for five weeks. Then we measured weight of body, ovaries. The histopathology changes of ovaries, and the expression of nerve growth factor(NGF) were also evaluated. Results: Single injection of EV induced suppression of weight gain, formation of cysts, increase of NGF expression. Oral administration of CR prevent suppression of weight gain shown in control group. In addition CR group showed upward tendency of ovarian size. Formation of cystic follicles induced by EV injection is suppressed by CR treatment. In additon, CR treatment lowered expression levels of nerve growth factor(NGF), which were elevated by induction of PCOS. Conclusion: These results suggest that CR can be used for patients with PCOS to prevent formation of cystic follicles and malfunction of ovary. And also suggest that the related mechanisms are involved in suppression of NGF expression.

자살을 시도한 우울증 환자에서 혈장 ${\beta}$-Nerve Growth Factor 농도의 변화 (Alteration of Plasma ${\beta}$-Nerve Growth Factor Concentration in Depressed Patients with Suicidal Attempt)

  • 심세훈;원성두;이분희;한창수;양종철;권영준;김용구
    • 생물정신의학
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    • 제13권2호
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    • pp.95-102
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    • 2006
  • Object : Nerve growth factor(NGF) is a protein involved in neuronal survival and plasticity in the central nervous system, which might play an important role in stress, depression and suicide. This study was performed to determine whether there is an alteration in plasma NGF concentrations in depressed patients with suicidal attempt. Methods : The subjects were 32 depressed patients who attempted suicide and admitted in emergency room. Forty-four hospitalized non-suicidal depressive patients and the 30 normal controls were closely matched with the suicidal group in terms of age and sex. Individuals in all 3 groups were evaluated independently by a semi-structured interview for the purpose of establishing a DSM-IV criteria diagnosis. The severity of depressive symptoms was evaluated using Hamilton depression rating scale(HDRS). The severity of the suicidal behavior was evaluated by Weisman and Worden's risk-rescue rating(RRR) system and the Lethality Suicide Attempt Rating Scale(LSARS). Plasma NGF level was measured by the enzyme linked immunosorbent assay(ELISA) method. Results : There were no statistically significant differences of the plasma NGF levels among groups. LSARS and RRR did not reveal any significant correlation with ${\beta}$-NGF level in suicidal depressive patients. Conclusion : This study do not support an association between ${\beta}$-NGF and suicidal depression. However it is necessary to investigate this association through other route such as postmortem brain.

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알코올 의존 환자에서 탄수화물결핍 트랜스페린과 신경성장인자의 변화 (The Alteration of Carbohydrate-Deficient Transferrin and Nerve Growth Factor in the Patients with Alcohol Dependence)

  • 전찬민;박병양;변정현;이병철;함병주;허미나;최인근
    • 생물정신의학
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    • 제14권3호
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    • pp.161-166
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    • 2007
  • Objectives:Recent studies have raised the possibility that nerve growth factor(NGF) is abnormally regulated in the central nervous system(CNS) of animal models with alcohol dependence. The possible alteration of NGF by prolonged alcohol intake may play an important role in alcohol-induced neurotoxicity. Carbohydrate-deficient transferrin(CDT) is regarded as a reliable biological marker of alcohol dependence. The goal of this study was to estimate the changes of %CDT and serum NGF level according to the duration of alcohol abstinence, and to identify whether %CDT level is associated with the serum NGF level in the patients with alcohol dependence. Methods:The subjects were 24 patients with alcohol dependence. We used the Axis-Shield ASA to measure the %CDT level and the enzyme-linked immunosorbent assay(ELISA) to measure the serum NGF level. %CDT and NGF levels were measured immediately after the admission and at 2 weeks after the admission. Results:Decreased %CDT were observed during the period of 2 weeks after the admission. NGF level was not significantly different after 2 weeks. The NGF levels were not correlated with %CDT. The possibility of %CDT as a predictor of alcohol-induced neurotoxicity was not confirmed. Conclusion:Serum NGF levels is not a reliable indicator of abstinence state in the patients with alcohol dependence. Further studies are needed to evaluate the relation between two indicators in regard to hematological and neurological changes in alcohol dependence.

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Estradiol valerate에 의해 유발되는 다낭성난소증후군의 Nerve Growth Factor 변화 (Expression of Nerve Growth Factor in Estradiol Valerate-induced Polycystic Ovary Syndrome)

  • 김세은;임성철;정문진;최백동;김승현;고아라;서승용;강성수;문창종;김종춘;김성호;배춘식
    • 한국임상수의학회지
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    • 제28권4호
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    • pp.403-407
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    • 2011
  • A form of polycystic ovary (PCO) resembling some aspects of the human PCO syndrome (PCOS) can be induced in rats by a single injection of estradiol valerate (EV). An increase in sympathetic outflow to the ovary precedes, by several weeks, the appearance of cysts, suggesting the involvement of a neurogenic component in the pathology of this ovarian dysfunction. To test the hypotheses that the change in sympathetic tone is related to an augmented production of hippocampal and/or ovarian nerve growth factor (NGF), and that this abnormally elevated production of NGF contributes to the induction of PCOS induced by EV. The animals were sacrificed after PCOS induction and the ovaries and hippocampus were sectioned and compared to the normal control. The expression of NGF was measured by immunohistochemical staining and Western blot analysis in the ovaries and hippocampus. EV-induced PCOS showed significant increase of ovarian NGF expression. Immunohistochemical expression of NGF was confined to the follicular cells and interstitial cells. Hippocampal NGF expression was not significantly changed. In conclusion EV-induced PCOS was related to the ovarian sympathetic activation which was mediated by NGF.

The Role of nerve Growth Factor on Corneal Wound Healing in Dogs

  • 우흥명
    • 한국임상수의학회지
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    • 제18권4호
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    • pp.418-423
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    • 2001
  • 각막상피의 창상치유에 중요한 역할을 하는 것으로 알려진 Nerve Growth Factor(NGF)의 내인성 변화와 국소적 투여효과를 알아보았다. 6마리의 Beagle 을 사용하여 비교군인 오른쪽 눈에만 6mm의 기계적인 각막 창상을 만들었고 왼쪽 눈은 대조군으로 사용하였다. 눈물은 수술후 1주일동안 매일, 각막 상피는 수술중 그리고 수술후 7일에 각각 채취하여 NGF 농도를 enzyme-linked immunosorbent assay (ELISA)를 사용하여 측정하였다. 2차 실험으로, 16마리의 Bealgle을 사용하여 오른쪽 눈에 위와 동일한 창상을 만든 후, 창상 부위가 회복될 때까지 recombinant human (rh) NGF (n=4), murine NGF (n=6) 그리고 anti-NGF blocking antibody (n=6)를 6시간마다 점안하였으며, 왼쪽 눈은 bovine serum albumin (BSA)를 점안하여 대조군으로 사용하였다. 창상 면적은 NIH image software를 이용하여 분석하였다. 대조군에 비하여, 비교군의 눈물내 NGF는 치유초기에 현저하게 증가하였으며, 각막 상피의 NGF도 유의적인 증가를 보였다. 그러나 rh NGF, murine NGF, anti-NGF blocking antibody처치군과 BSA처치군 간에는 각막창상 치유에 유의적인 차이가 인정되지 않았다. 각막창상후, rh NGF 혹은 murine NGF의 추가적인 국소점안은 정상개의 각막상피 치유에 효과가 없었으나, 창상후 초기 치유기동안 눈물과 손상받은 각막상피에서 내인성 NGF의 급격한 보상성 증가로 미루어 NGF는 각막 상피의 창상치유에 중요한 역할을 하는 것으로 사료된다.

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Nerve Growth Factor Activates Brain-derived Neurotrophic Factor Promoter IV via Extracellular Signal-regulated Protein Kinase 1/2 in PC12 Cells

  • Park, So Yun;Lee, Ji Yun;Choi, Jun Young;Park, Mae Ja;Kim, Dong Sun
    • Molecules and Cells
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    • 제21권2호
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    • pp.237-243
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    • 2006
  • Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.

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.