• Title/Summary/Keyword: neurotrophic factors

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Neural Ablation and Regeneration in Pain Practice

  • Choi, Eun Ji;Choi, Yun Mi;Jang, Eun Jung;Kim, Ju Yeon;Kim, Tae Kyun;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • v.29 no.1
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    • pp.3-11
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    • 2016
  • A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration.

The Effects of Exercise on Neurotrophins, Hepatocyte Growth Factor (HGF), and Oxidative Stress in Obese Children (운동 트레이닝이 비만 어린이의 neurotrophins, HGF (hepatocyte growth factor)와 산화스트레스에 미치는 영향)

  • Woo, Jin-Hee
    • Journal of Life Science
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    • v.22 no.5
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    • pp.569-574
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    • 2012
  • This study was conducted to investigate the effect of exercise on oxidative stress, nerve growth, and hepatocyte growth factors in obese children. After 12 weeks of aerobic exercise training, the aforementioned parameters before and after the training were compared. As a result, the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were shown to be lower in the OT than in the NT before and after the training, respectively ($p$ <0.05). The NGF was shown to have increased in both groups after the training ($p$ <0.05). The hepatocyte growth factor (HGF) was shown to be higher in the OT than in the NT before the training ($p$ <0.05), with no difference found afterwards. The malondialdehyde (MDA), ox-LDL, and 8-OHdG (Oxo-2'-deoxyguanosine) were shown to be higher in the OT than in the NT ($p$ <0.05). For ox-LDL, a difference was found between before and after the training ($p$ <0.05). The results of this study showed that obesity induced oxidative stress and caused the abnormalities of nerve and HGF secretion in obese children, and that the 12 weeks of aerobic exercise increased NGF levels, thereby promoting the development of neurogenesis in children.

Protective Effects of Combination of Carthamus tinctorius L. Seed and Taraxacum coreanum on Scopolamine-induced Memory Impairment in Mice (홍화씨와 흰민들레 복합물의 Scopolamine 유도 기억력 손상에 대한 보호 효과)

  • Kim, Ji Hyun;He, Mei Tong;Kim, Min Jo;Park, Chan Hum;Lee, Jae Yang;Shin, Yu Su;Cho, Eun Ju
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.2
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    • pp.85-94
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    • 2020
  • Background: Alzheimer's disease (AD) is caused by various factors, such as cholinergic dysfunction, regulation of neurotrophic factor expression, and accumulation of amyloid-beta. We investigated whether or not a combination of Carthamus tinctorius L. seed and Taraxacum coreanum (CT) has a protective effect on scopolamine-induced memory impairment in a mouse model. Methods and Results: Mice were orally pretreated with CT (50, 100 and 200 mg/kg/day) for 14 days, and scopolamine (1 mg/kg/day) was injected intraperitoneally before subjecting them to behavior tests. CT-administered mice showed better novel object recognition and working memory ability than scopolamine-treated control mice. In T-maze and Morris water maze tests, CT (100 and 200 mg/kg/day) significantly increased space perceptive ability and occupancy to the target quadrant, respectively. In addition, 100 and 200 mg/kg/day of CT attenuated cholinergic dysfunction through inhibition of butyryl cholinesterase in brain tissue. Furthermore, CT-administered mice showed higher cyclic adenosine monophosphate-response element-binding protein (CREB) levels and lower amyloid precursor protein (APP) levels compared to scopolamine-treated control mice. Conclusions: CT improved scopolamine-induced memory impairment through inhibition of cholinergic dysfunction, up-regulation of CREB, and down-regulation of APP. Therefore, CT could be a useful therapeutic agent for AD with protective effects on cognitive impairment.

Genistein attenuates isoflurane-induced neurotoxicity and improves impaired spatial learning and memory by regulating cAMP/CREB and BDNF-TrkB-PI3K/Akt signaling

  • Jiang, Tao;Wang, Xiu-qin;Ding, Chuan;Du, Xue-lian
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.579-589
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    • 2017
  • Anesthetics are used extensively in surgeries and related procedures to prevent pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular anesthetic exposure. Recent studies have indicated that brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes. Genistein, a plant-derived isoflavone, has been shown to exhibit neuroprotective effects. The present study was performed to examine the protective effect of genistein against isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered genistein at doses of 20, 40, or 80 mg/kg body weight from P3 to P15 and then exposed to isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following isoflurane exposure. Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced BDNF and TrkB mRNA levels. Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated. Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that genistein exerts neuroprotective effects by suppressing isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-BDNF-TrkB-PI3/Akt signaling.

XENOTRANSPLANT OF HUMAN BONE MARROW STROMAL CELLS; EFFECT ON THE REGENERATION OF AXOTOMIZED INFRAORBITAL NERVE IN RATS (인간 골수 기질세포 이종이식이 백서의 축삭절단 안와하 신경 재생에 미치는 효과)

  • Park, Eun-Jin;Kim, Eun-Seok;Kim, Jin-Man;Kim, Hyun-Ok;Yum, Kwang-Won
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.31 no.3
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    • pp.239-247
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    • 2005
  • This study demonstrated that xenogenic human marrow mesenchymal stem cells (hMSCs) could elicit the regeneration of the sensory nerve after axotomy in the adult rats infraorbital nerves without immunosuppression. For this, we evaluated the behavioral testing for functional recovery of the nerve and histological findings at weeks 3 and 5 compared to controls. Xenogenic hMSCs did not evoke any significant inflammatory or immunologic reaction after systemic and local administrations. HMSCs-treated rats exhibited significant improvement on sensory recovery tested with von Frey monofilaments. At 5 postoperative weeks, in the hMSCs treated nerve, expression of myelin basic protein (MBP), neurofilament (NF) at the site of axotomy was higher than control. And mRNA expression of neurotropin receptor Trk precursor (TrkPre), nerve growth factor receptor (NGFR) and neuropeptide (NPY) in trigeminal ganglion were also higher. The number of myelinated nerve at distal stump and cells in trigeminal ganglion were higher in hMSC treated rats. So it was supposed that transplanted MSCs contributed to reducing post-traumatic degeneration and production of neurotrophic factors. Immunofluorescence labeling showed small portion of hMSCs (<10%) expressed a phenotypic marker of Schwann cell (S-100). Xenogenic or allogenic mesenchymal stem cells might have immune privileged characteristics and useful tool for cell based nerve repair.

Identification of Niche Conditions Supporting Short-term Culture of Spermatogonial Stem Cells Derived from Porcine Neonatal Testis

  • Park, Min Hee;Park, Ji Eun;Kim, Min Seong;Lee, Kwon Young;Yun, Jung Im;Choi, Jung Hoon;Lee, Eunsong;Lee, Seung Tae
    • Journal of Embryo Transfer
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    • v.29 no.3
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    • pp.221-228
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    • 2014
  • Despite that porcine spermatogonial stem cells (pSSCs) have been regarded as a practical tool for preserving eternally genetic backgrounds derived from pigs with high performance in the economic traits or phenotypes of specific human diseases, there were no reports about precise definition of niche conditions promoting proliferation and maintenance of pSSCs. Accordingly, we tried to determine niche conditions supporting proliferation and maintenance of undifferentiated pSSCs for short-term. For these, undifferentiated pSSCs were progressively cultured in different composition of culture medium, seeding density of pSSCs, type of feeder cells and concentration of growth factors, and then total number of and alkaline phosphatase (AP) activity of pSSCs were investigated at post-6 day culture. As the results, the culture of $4{\times}10^5$ pSSCs on mitotically in activated $2{\times}10^5$ STO cells in the mouse embryonic stem cell culture medium (mESCCM) supplemented with 30 ng/ml glial cell line-derived neurotrophic factor (GDNF) was identified as the best niche condition supporting effectively the short-term maintenance of undifferentiated pSSCs. Moreover, the optimized short-term culture system will be a basis for developing long-term culture system of pSSCs in the following researches.

Therapeutic Potential of Active Components from Acorus gramineus and Acorus tatarinowii in Neurological Disorders and Their Application in Korean Medicine

  • Cheol Ju Kim;Tae Young Kwak;Min Hyeok Bae;Hwa Kyoung Shin;Byung Tae Choi
    • Journal of Pharmacopuncture
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    • v.25 no.4
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    • pp.326-343
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    • 2022
  • Neurological disorders represent a substantial healthcare burden worldwide due to population aging. Acorus gramineus Solander (AG) and Acorus tatarinowii Schott (AT), whose major component is asarone, have been shown to be effective in neurological disorders. This review summarized current information from preclinical and clinical studies regarding the effects of extracts and active components of AG and AT (e.g., α-asarone and β-asarone) on neurological disorders and biomedical targets, as well as the mechanisms involved. Databases, including PubMed, Embase, and RISS, were searched using the following keywords: asarone, AG, AT, and neurological disorders, including Alzheimer's disease, Parkinson's disease, depression and anxiety, epilepsy, and stroke. Meta-analyses and reviews were excluded. A total of 873 studies were collected. A total of 89 studies were selected after eliminating studies that did not meet the inclusion criteria. Research on neurological disorders widely reported that extracts or active components of AG and AT showed therapeutic efficacy in treating neurological disorders. These components also possessed a wide array of neuroprotective effects, including reduction of pathogenic protein aggregates, antiapoptotic activity, modulation of autophagy, anti-inflammatory and antioxidant activities, regulation of neurotransmitters, activation of neurogenesis, and stimulation of neurotrophic factors. Most of the included studies were preclinical studies that used in vitro and in vivo models, and only a few clinical studies have been performed. Therefore, this review summarizes the current knowledge on AG and AT therapeutic effects as a basis for further clinical studies, and clinical trials are required before these findings can be applied to human neurological disorders.

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

  • Seo, Jeongpyo;Heo, Junhoe;Kim, Hyunjun;Park, Jangjun
    • Journal of The Korean Society of Integrative Medicine
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    • v.8 no.1
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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.

The Effects of Sustained Release Growth Hormone in the Repair of Neurological Deficits in Rats with the Spinal Cord Injury (척수손상 백서에서 서방형 성장호르몬의 투여가 신경회복에 미치는 영향)

  • Kim, Min Su;Heo, Jung;Kwon, Yong Seok;Lee, Keun Cheol;Kim, Seok Kwun
    • Archives of Plastic Surgery
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    • v.35 no.3
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    • pp.235-242
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    • 2008
  • Purpose: Due to increasing interest in the treatment of spinal cord injuries, many histopathological studies have been conducted to prove that many neurotrophic factors including growth hormone are important for regeneration of the injured spinal cord. Growth hormone has to be given everyday, however, and this negatively affects compliance in clinical trials. Recently, the invention of sustained release growth hormone (SRGH) that can be given just once a week may both help the regeneration of injured spinal cord and, at the same time, be more compliant and convenient for clinical patients. Methods: In this study, thirty 7-week-old female Spraque-Dawley rats were subjected to a weight-driven impact spinal cord injury. They were divided into 3 groups and Group I and II were injected with SRGH once a week for 4 weeks; Group I were injected into the injured spinal cord area, while Group II were injected into the peritoneal cavity. Meanwhile, Group III were injected with normal saline solution. The functional outcome was evaluated using the Basso-Beattie-Bresnahan motor rating score and the inclined plane test was done 4 weeks after the first injection. Histopathological examination was performed at the same time and the amount of residual white matter was measured in all groups. Results: After 4 weeks, Groups I and II showed greater improvement than Group III(the control group) in the functional test. In the control group, invasion of atypical phagocytes, axonal degeneration, edema and cavity formation in the posterior site of spinal cord gray matter was observed in histopatholgical examination. The rate of residual white matter in Group III was less than in the other groups. Conclusion: Data showed significant functional and histopathological improvement in the groups treated with SRGH into the spinal and peritoneal cavity compared with the control group. SRGH is therefore beneficial because it helps with regeneration of the injured spinal cord and improves the compliance and convenience of patients.

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.