• ALGAE
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• 제31권1호
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• pp.73-84
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• 2016

Marine organisms are frequently used to be harmful and have lower side effects than synthetic drugs. The cognitive improving efficacy of gamma aminobutyric acid-enriched fermented Saccharina japonica (FSJ) on the memory deficient rats, which were induced by trimethyltin chloride (TMT), was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), cAMP response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) immunohistochemistry. The neurite outgrowth of Neuro2a cells was assessed in order to examine the underlying mechanisms of the memory enhancing effects of FSJ. Treatment with FSJ tended to shorten the latency to find the platform in the acquisition test of the Morris water maze at the second and fourth day compared to the control group. In the probe trial, the FSJ treated group increased time spent in the target quadrant, compared to that of the control group. Consistent with the behavioral data, these treatments recovered the loss of ChAT, CREB, and BDNF immunepositive neurons in the hippocampus produced by TMT. Treatment with FSJ markedly stimulated neurite outgrowth of the Neuro2a cells as compared to that of the controls. These findings demonstrate that FSJ may be useful for improving the cognitive function via regulation of neurotrophic marker enzyme activity.

• 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.

• 생명과학회지
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• 제22권11호
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• pp.1444-1450
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• 2012

본 연구의 목적은 1회성 축구활동이 남자 청소년의 혈청 뉴로트로핀 수준과 신경인지 기능에 미치는 영향을 규명하는데 있다. 연구의 대상은 건강한 남자 청소년 15명으로 하였으며, 연구 대상은 축구활동 처치(SOC) 조건과 자율학습 처치(CON) 조건의 2가지 처치 조건에 참여하였다. 채혈은 처치 전(Pre), 처치 후(Post), 처치 후 2시간(Post-2 h) 시점에서 총 3회 실시하였으며, 채취된 혈액을 이용하여 혈청 serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1)을 분석하였다. 신경인지 기능의 평가는 Stroop 색체-단어 검사를 이용하였으며, 채혈 시점과 동일한 시점에서 측정하였다. 연구 결과, 혈청 BDNF, NGF, IGF-1 수준은 축구활동 후 유의하게 증가하였으며(p<0.05), Post 시점에서 SOC 조건이 CON 조건과 비교하여 유의하게 높게 나타났다(p<0.05). Stroop 색체-단어 검사는 색체-단어 검사 점수에서 축구활동 후 유의한 증가를 나타내었으며(p<0.05), Post 시점과 Post-2 h 시점에서 SOC 조건이 CON 조건과 비교하여 유의하게 높게 나타났다(p<0.05). 이상의 결과를 종합하면, 1회성 축구활동이 뉴로트로핀을 증가시켜 신경인지 기능에 긍정적 영향을 나타낸 것으로 판단된다.

• Journal of Applied Biological Chemistry
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• 제65권1호
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• pp.23-31
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• 2022

Oxidative stress and neuroinflammation play important roles in the pathogenesis of Alzheimer's disease (AD). This study investigated the protective effects of paeoniflorin (PF) against neuronal oxidative stress and neuroinflammation in lipopolysaccharide (LPS)-induced mice. The brains of LPS-injected control group showed significantly increased neuroinflammation by activating the nuclear factor kappa B (NF-κB) pathway and increasing inflammatory mediators. However, administration of PF significantly attenuated oxidative stress by inhibiting lipid peroxidation, nitric oxide levels, and reactive oxygen species production in the brain; PF at doses of 5 and 10 mg/kg/day downregulated the expression of NF-κB pathway-related proteins and significantly decreased inflammatory mediators including inducible nitric oxide synthase and cyclooxygenase-2. Moreover, the levels of brain-derived neurotrophic factor and its receptor, tropomycin receptor kinase B, were significantly increased in PF-treated mice. Furthermore, acetylcholinesterase activity and the ration of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X were significantly reduced by PF in the brains of LPS-induced mice, resulting in the inhibition of cholinergic dysfunction and neuronal apoptosis. Thus, we can conclude that administration of PF to mice prevents the development of LPS-induced AD pathology through the inhibition of neuronal oxidative stress and neuroinflammation, suggesting that PF has a therapeutic potential for AD.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권3호
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• pp.199-218
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• 2005

Purpose of Study: Peripheral nerve regeneration depends on neurotrophism of distal nerve stump, recovery potential of neuron, supporting cell like Schwann cell and neurotrophic factors such as BDNF. Peripheral nerve regeneration can be enhanced by the conduit which connects the both sides of transected nerve. The conduit maintains the effects of neurotrophism and BDNF produced by Schwann cells which can be made by gene therapy. In this study, we tried to enhance the peripheral nerve regeneration by using calcium phosphate coated porous conduit and BDNF-Adenovirus infected Schwann cells in sciatic nerve of rats. Materials and Methods: Microporous filter which permits the tissue fluid essential for nerve regeneration and does not permit infiltration of fibroblasts, was made into 2mm diameter and 17mm length conduit. Then it was coated with calcium phosphate to improve the Schwann cell adhesion and survival. The coated filter was evaluated by SEM examination and MTT assay. For effective allogenic Schwann cell culture, dorsal root ganglia of 1-day old rat were extracted and treated with enzyme and antimitotic Ara-C. Human BDNF cDNA was obtained from cDNA library and amplified using PCR. BDNF gene was inserted into adenovirus shuttle vector pAACCMVpARS in which E1 was deleted. We infected the BDNF-Ad into 293 human mammary kidney cell-line and obtained the virus plaque 2 days later. RT-PCR was performed to evaluate the secretion of BDNF in infected Schwann cells. To determine the most optimal m.o.i of BDNF-Ad, we infected the Schwann cells with LacZ adenovirus in 1, 20, 50, 75, 100, 250 m.o.i for 2 hours and stained with ${\beta}$-galactosidase. Rats(n=24) weighing around 300g were used. Total 14mm sciatic nerve defect was made and connected with calcium phosphate coated conduits. Schwann cells$(1{\times}10^6)$ or BDNF-Ad infected Schwann cells$(1{\times}10^6)$ were injected in conduit and only media(MEM) was injected in control group. Twelve weeks after surgery, degree of nerve regeneration was evaluated with gait analysis, electrophysiologic measurements and histomorphometric analysis. Results: 1. Microporous Millipore filter was effective conduit which permitted the adhesion of Schwann cells and inhibited the adhesion of fibroblast. We could enhance the Schwann cell adhesion and survival by coating Millipore filter with calcium phosphate. 2. Schwann cell culture technique using repeated treatment of Ara-C and GDNF was established. The mean number of Schwann cells obtained 1 and 2 weeks after the culture were $1.54{\pm}4.0{\times}10^6$ and $9.66{\pm}9.6{\times}10^6$. 3. The mRNA of BDNF in BDNF-Ad infected Schwann cells was detected using RT-PCR. In Schwann cell $0.69\;{\mu}g/{\mu}l$ of DNA was detected and in BDNF-Adenovirus transfected Schwann cell $0.795\;{\mu}g/{\mu}l$ of DNA was detected. The most effective infection concentration was determined by LacZ Adenovirus and 75 m.o.i was found the most optimal. Conclusion: BDNF-Ad transfected Schwann cells successfully regenerated the 14mm nerve gap which was connected with calcium phosphate coated Millipore filter. The BDNF-Ad group showed better results compared with Schwann cells only group and control group in aspect to sciatic function index, electrophysiologic measurements and histomorphometric analysis.

• 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.

• Journal of Microbiology and Biotechnology
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• 제33권9호
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• pp.1189-1196
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• 2023

This study proposed to demonstrate the neuroprotective effects of heat-killed Levilactobacillus brevis KU15152. Heat-killed L. brevis KU15152 showed antioxidant activity similar to that of Lacticaseibacillus rhamnosus GG, in terms of radical scavenging activity. To evaluate the neuroprotective effects, conditioned medium (CM) obtained by incubating heat-killed bacteria in intestinal cells (HT-29) was used through gut-brain axis. CM from L. brevis KU15152 protected neuroblastoma cells (SH-SY5Y) against H₂O₂-induced oxidative stress. Pretreatment with CM significantly alleviated the morphological changes induced by H₂O₂. Heat-killed L. brevis KU15152 showed an increased brain-derived neurotrophic factor (BDNF) expression in HT-29 cells. L. brevis KU15152-CM remarkably downregulated the Bax/Bcl-2 ratio, while upregulating the expression of BDNF and tyrosine hydroxylase (TH) in SH-SY5Y cells. Furthermore, L. brevis KU15152-CM reduced caspase-3 activity following H₂O₂ treatment. In conclusion, L. brevis KU15152 can be potentially used as food materials to avoid neurodegenerative diseases.

• 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.

• 생명과학회지
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• 제22권9호
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• pp.1231-1236
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• 2012

비만은 여러 가지 질환을 유발하는데 이중에서도 뇌신경세포의 활성 및 생성에도 부정적인 영향을 미치는 것으로 보고되고 있어 이에 대한 추가적인 연구가 필요하다. 본 연구는 과체중 및 비만 청소년의 BDNF 개선을 위한 운동 효과를 검증하고자 12주 복합운동에 따른 신체구성, 혈중지질, BDNF의 변화를 분석하였다. 이를 위해 과체중 및 비만 청소년 18명을 복합운동군 9명, 대조군 9명으로 무선표집하여 연구를 진행하였다. 연구 결과 통계적으로 집단간 차이를 보이며 체중(p<0.01), BMI (p<0.05), 체지방률(p<0.05), 체지방량(p<0.01)이 감소하고, 제지방률(p<0.05)이 증가하였다. 또한 TC와 LDL-C의 평균은 운동군이 대조군보다 더 많은 감소 경향을 나타내었고, HDL-C는 두 집단 모두 감소하는 경향을 보였으나 모두 집단간 차이는 나타나지 않았다. 또한 BDNF의 평균은 운동군이 대조군보다 더 많은 증가 경향을 나타내었으나 집단간 차이는 나타나지 않았다. 본 연구를 통하여 12주 복합운동 프로그램은 과체중 및 비만 남자 청소년의 체중, BMI, 체지방률, 체지방량, 제지방률은 개선시킬 수 있으나 혈중 지질 및 BDNF의 변화에는 영향을 미치지 못하는 것을 알 수 있었다. 본 연구를 통하여 12주 복합운동 프로그램은 과체중 및 비만 남자 청소년의 체중, BMI, 체지방률, 체지방량, 제지방률은 개선시킬 수 있으나 혈중 지질 및 BDNF의 변화에는 영향을 미치지 못하는 것을 알 수 있었다.

• 생명과학회지
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• 제19권4호
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• pp.449-456
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• 2009

신경아세포종은 미분화된 신경외배엽 세포로부터 유래한 신경능세포에 의해 형성된 소아기에 보는 가장 많이 발생하는 악성 종양 중 하나이다. 신경아세포종인 Neuro-2a 세포는 신경세포의 분화, 세포사 억제 효능, 세포독성 검정 등에 활용되고 있다. Neuro-2a 역시 다른 신경아세종과 같이 염색체 변이를 가지고 있지만, 이에 대해 고밀도의 게놈수준에서 염색체 변이에 대해 보고된 바가 없다. 본 연구에서는 고집적 마이크로어레이(최소 43,000 개의 코딩, non-코딩 유전자 서열이 집적된 마이크로어레이)기반의 비교유전체보합법을 활용하여, 고해상도의 Neuro-2a 유전체 이상을 분석하였다. 마이크로 어레이 데이터는 Hidden Markov Model을 활용하여, 유전체 변이를 double loss, single loss, normal, single gain 그리고 amplification으로 나누어 분석하였다. Neuro2a는 MYCN 유전자의 증폭은 관찰되지 않았고, GDNF, BDNF, NENF등의 neurotrophic factor 가운데 NENF의 gain 현상이 관찰 되었다. 염색체의 이상은 4,8,10,11,15번에서 발견되었으며, 염색체 3,17,18,19에서는 전부 20개 미만의 염색체 이상이 발견되었다. 염색체 이상이 연속적으로 일어난 부위 중 gain으로서 가장 긴 부분은 Chr8:8,427,841-35,162,415의 약 26.7 Mb이며, single loss로서 가장 긴 곳은 Chr4:73,265,785-88,374,165의 약 15.1 Mb였다. 염색체의 위치는 UCSC 데이터베이스 (UCSC mm8, NCBI Build 36)에 근거하였다.