• 대한의생명과학회지
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• 제30권1호
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• pp.1-9
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• 2024

Although there have been several attempts to use virtual reality (VR) in the treatment of depression, the results have been inconsistent and existing studies have mostly relied on subjective measures to assess the effectiveness of VR in improving depression. The aim of this study was to investigate the effect of nature experience-based VR intervention on depressive symptoms in a young population using both subjective and objective measurements. The study population included 15 participants who had more than 14 identifiers of the Korean Beck Depression Inventory (K-BDI)-II. Participants received three weeks (four times per week) of VR intervention. The effectiveness of VR was assessed through changes in K-BDI-II scores and depression-related blood biomarkers. Nature experience-based VR intervention led to an approximately 50% reduction of K-BDI-II score (before 25.7±7.7 vs. after 12.5±8.3 (P<0.001)). Of these, loss of pleasure and fatigue showed the largest amount of improvement. However, levels of cortisol, brain-derived neurotrophic factor, and interleukin-6 did not differ from those at baseline. The findings of our pilot study suggest that nature experience-based VR can be a useful adjunctive treatment method for improving depressive symptoms in individuals who have difficulty accessing the real outside natural environment.

• Biomolecules & Therapeutics
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• 제21권4호
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• pp.299-306
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• 2013

In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.

• 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.

• Nutrition Research and Practice
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• 제12권3호
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• Applied Microscopy
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• 제39권1호
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• pp.1-7
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• 2009

사람에서의 PCO와 몇몇 측면에서 유사한, 실험적으로 유발된 다낭성난소(polycystic ovary, PCO)는 장기간 작용하는 estradiol valerate (EV)에 의해 유발된다. 랫드에서 스테로이드로 유발한 PCO 모델에서 홍삼 총사포닌의 역할에 대한 우리의 이전연구는 전침이 난소의 nerve growth factor (NGF) 농도를 조절하는 것을 검증하였다. 실제로 PCO와 관련된 난소 기능부전의 병리기전에서 신경성 요소의 관련성은 난소로의 교감신경유출(sympathetic outflow)의 증가로 인해 높아진다. 따라서 본 연구에서는 치료제로서의 GTS 투여가 PCO를 유발한 랫드에서 교감신경 활성을 조절할 것이라는 가설을 시험해보고자 하였다. 본 연구에서는 스테로이드로 유발한 PCO에 내재하고 있는 병태생리학적 과정과 연관된 NGF 단백질과 NGF mRNA를 분석함으로써 이루어졌다. PCO가 유발된 랫드에서 EV 대조군은 oil 대조군과 비교하였을 때 유의적으로 높은 NGF mRNA의 발현을 나타내었으며, GTS 투여군은 EV 대조군에 비해 유의적으로 낮은 NGF mRNA의 발현을 나타내었다. 그러나 NGF 단백질은 oil 대조군에 비해 EV 대조군과 GTS 투여군에서도 유의적인 변화를 발견할 수 없었다. 이러한 결과는 EV가 설치류에서 낭종 형성과 무배란을 유발하는 병리학적 단계의 구성요소일 수 있는 난소의 신경향성 단계(neurotrophic state)를 조절한다고 생각할 수 있다.

• 한국콘텐츠학회논문지
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• 제11권4호
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• pp.273-282
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• 2011

본 연구는 국소 허혈성 뇌손상 흰쥐 모델에서 tDCS의 자극 적용시간을 달리하였을 때, 앞다리 운동감각 기능변화와 신경영양인자(GAP-43)발현에 미치는 영향을 알아보고자 하였다. 뇌손상 모델은 Sprague -Dawley계 흰쥐 80마리를 'Longa'방법을 이용하여 중대뇌동맥(middle cerebral artery)을 폐색하여 유발하였고, 실험군을 4개로 나누었다; 실험군I은 허혈성 뇌손상 유발군(n=20), 실험군II는 허혈성 뇌손상 유발 후 tDCS(10분) 적용군(n=20), 실험군III은 허혈성 뇌손상 유발 후 tDCS(20분) 적용군(n=20), 실험군IV는 허혈성 뇌손상 유발 후 tDCS(30분) 적용군(n=20)으로 나누었다. 앞다리운동감각 기능검사를 위해 수정된 앞다리배치 검사와 단일 팰릿 닿기 검사를 실시하였으며, 신경가소성에 대한 면역조직화학적 검사로 운동감각 영역에서의 GAP-43 단백질 발현을 관찰하였다. 앞다리운동감각 검사는 14일에서 실험군III (p<0.05)이 다른 군들에 비해 유의한 차이를 보였으며, 단일 팰릿 닿기 검사는 14일에서 실험군III(p<0.01)과 실험군IV(p<0.05)에서 유의한 차이를 보였다. 또한, 면역조직학적 검사는 14일에 실험군III이 다른 군들에 비해 현저한 면역양성반응의 증가를 보였다. 따라서, 0.1 mA의 강도로 20분간 적용했을 때가 앞다리운동감각 기능과 신경가역성 인자 GAP-43 발현에 가장 좋은 조건임을 알 수 있었다.

• 한국식품영양과학회지
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• 제42권10호
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• pp.1585-1591
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• 2013

본 연구의 목적은 고지방식으로 유도된 비만이 에너지 항상성 조절인자인 신경영양인자와 섭식조절 호르몬인 렙틴 mRNA 발현에 어떠한 관련성이 있는지를 규명하는 것과 비만 쥐의 시상하부 BDNF 발현과 렙틴 리셉터 mRNA 발현, 혈청 렙틴과 항비만과의 관계에 대한 운동트레이닝과 정상식이로의 전환에 대한 효과를 확인하고자 하였다. 그 결과 8주 후 비만 대조군(HF)에 비해 운동군(HFT), 정상식이군(HFND), 운동 및 정상식이 트레이닝군(HFNDT)에서 각각 유의한 체중 및 혈중 TC 감소를 보였다(P<0.05). 혈중 TG에서는 HF군에 비해 HFNDT군에서 유의한 감소를 보였다(P<0.05). 혈중 렙틴은 HF군에 비해 HFT군에서 유의한 감소를(P<0.05), HFT군에 비해 HFND군에서 유의한 감소를 보였으며(P<0.05), HFND군에 비해 HFNDT군에서 유의한 감소를 나타냈다(P<0.05). 시상하부 BDNF 단백질 발현은 HF군에 비해 모든 군에서 유의한 증가를 보였다(P<0.05). 시상하부 렙틴 리셉터 mRNA는 HF군에 비해 HFT와 HFND군에서 약간의 감소를, HFNDT군에서는 증가를 나타내었다. 이상의 결과는 고지방식이로 유도된 비만쥐에 대한 운동트레이닝은 항비만 효과가 있는 것으로 나타났으며, 운동 또는 정상식이의 병행은 식욕과 체중조절에 최적의 비만예방 및 개선효과가 있을 것으로 사료된다.

• 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.

• 동의생리병리학회지
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• 제24권2호
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• pp.228-235
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• 2010

This study was performed to investigate the memory enhancing effect of Poria cocos Wolf (Hoelen cum radix) against scopolamine-induced amnesia in Sprague-Dawley (SD) rats. To induce amnesia, scopolamine (0.75 mg/kg) was intraperitonically injected into SD rats 30 min before starting behavior tests. We have conducted Morris water-maze and Y-maze tests to monitor learning and memory functions. Poria cocos effectively reversed scopolamine-induced memory impairment in SD rats which was represented by an improvement of mean escape latency in water-maze test and spontaneous alterations in Y-maze test. To elucidate possible molecule mechanism, we have measured mRNA as well as protein expression of acetylcholine esterase (AchE), choline acetyltransferase (ChAT), muscarinic acetylcholine receptor (mAchR), and brain-derived neurotrophic factor (BDNF) using RT-PCR and Western blot analysis, respectively. Poria cocos increased mRNA levels of ChAT and mAchR in rat hippocampus compared with those in the scopolamine-injected amnesic group. In addition, protein expression of ChAT and BDNF was also elevated by Poria cocos intake. Furthermore, as an upstrem regulator, the activation of cAMP response element-binding protein (CREB) was assessed by immunohistochemistry. In this immunohistochemical analysis, the phosphorylation of CREB (p-CREB) was reduced by scopolamine injection, which was restored back to control levels by administration of Poria cocos. These results suggest that Poria cocos may improve memory and cognitive deficit in amnesia and have therapeutic potentials through up-regulation of ChAT, mAchR, and BDNF, which seemed to be mediated by activation of CREB.

• 한국식품과학회지
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• 제53권6호
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• pp.715-721
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• 2021

인구의 고령화에 따른 노인 인구 증가로 지난 10년간 치매환자수와 경도인지장애 환자수가 급증하였다. 치매는 예방이 중요한 만큼 인지기능 향상에 도움을 줄 수 있는 기능성 소재 탐색에 대한 연구가 필요하다. 한편, PGG는 다양한 약용식물에 함유되어있는 gallotannins로 소교세포에서 항염증효과, amyloid beta 단백질 침착 억제효과, beta-secretase 억제효과가 알려져 있으나 인지 기능과 관련된 지표들에 대한 연구는 부족한 실정이다. 이에 본 연구에서는 PGG가 신경모세포주인 SK-N-SH세포에서 인지기능과 관련된 인자에 미치는 영향을 검토하고 관련 기전에 대해 평가하였다. 퇴행성질환 등에서 그 분비가 증가되는 AChE 효소활성이 PGG 처리에 의해 시험관실험과 세포실험에서 모두 억제되었다. 또한, PGG는 neurotrophin 중의 하나인 BDNF mRNA 및 단백질 발현을 증가하였다. 이러한 PGG의 BDNF 발현 증가에 대한 분자적 기전을 확인하기 위해 CAMKII-CREB 신호경로를 측정한 결과, PGG는 CAMKII를 인산화하였고, BDNF의 전사인자인 CREB를 활성화하였다. 이상의 결과로부터, hydrolyzed tannins의 하나인 PGG가 신경세포에서 CAMKII-CREB 경로를 활성화함으로써 BDNF의 발현을 증가시킬 뿐만 아니라 AChE 활성을 억제하는 것으로 나타났다(Fig. 8). 추가적으로 이러한 PGG의 효과가 인지기능이 저하된 동물모델 등에서도 효과가 있는지를 검토할 필요가 있다. 이러한 자료가 축적이 된다면 향후 PGG가 인지기능 개선을 위한 기능성 소재로서의 사용될 가능성이 있을 것으로 생각된다.