• 생명과학회지
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• 제23권9호
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• pp.1096-1103
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• 2013

만성외상성뇌병증(Chronic traumatic encephalopathy, CTE)은 운동선수와 매우 밀접하게 관련되어 있으며 장기간에 걸쳐 반복적인 외상성뇌손상(traumatic brain injury, TBI)로 인한 퇴행성뇌질환이다. 신경영양인자(neurotrophic factor)는 여러 종류가 알려져 있으며 이들은 뇌와 척수의 물리적 손상시에 신경보호효과가 있다. 따라서, 신경영양인자의 혼합물인 cebrolysin을 이용하여 CTE질환에 가장 적합하다고 여겨지는 repetitive mild TBI (rmTBI) 모델에서 cerebrolysin의 신경보호효과를 알아보고자 하였다. 실험군은 5군(groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control)으로 나누어 진행하였다. CTE의 가장 대표적 표시인자인 tau 단백질의 인산화를 조직학적으로 조사한 결과, 대뇌겉질과 해마내 CA3 영역에서 phospho-tau단백질의 발현이 증가되었으며 cerebrolysin ($10{\mu}l$ of 1 mg/ml)를 미정맥으로 투여시 p-tau발현이 감소되었다. CTE의 병인으로 알려진 별아교세포와 미세아교세포의 활성을 각각의 표시인인 GFAP, iba-1을 이용하여 면역조직화학염색을 시행하였다. 별아교세포의 활성은 rmTBI에 의하여 증가하였으며 cerebrolysin에 의해 회복되었으나 미세아교세포의 활성은 관찰되지 않았다. 또한 rmTBI모델에서 체내 탐식세포(macrophage)의 뇌내유입유무를 관찰하고자 CD45 염색을 시행하였으나 유의한 차이를 관찰하지 못하였다. 이상의 결과를 종합하면, cerebrolysin이 rmTBI에 의한 tau단백질의 인산화 및 별아교세포의 활성을 조절하는 것으로 사료된다. 따라서 cerebrolysin이 CTE 환자에 대한 치료 약물의 후보가 될 수 있음을 시사한다.

• 생명과학회지
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• 제21권7호
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• pp.985-991
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• 2011

본 연구는 고지방식이로 인한 비만으로 불균형된 지질구성과 산화적 손상이 신경세포형성과 초기발현단백질에 미치는 생물학적 영향을 알아보고, 규칙적인 운동의 효과를 알아보기 위하여 실시하였다. 실험동물은 4주령 SD rat 수컷 30마리를 1주간의 적응기간을 둔 뒤, 15주간 고지방식이를 통해 비만으로 유도하였으며, high fat diet sedentary (HDS, n=15)와 high fat diet and training (HDT, n=15)으로 분류하여 연구하였다. 운동강도는 1~4주는 저강도, 5~8주는 중강도로 주5회 실시하였다. 8주 트레이닝 후 혈청지질, 8-OHdG, MDA, neurotrophic factor, 그리고 IEG를 분석하였다. 그 결과 TC와 TG에서 HDS와 HDT 사이 유의한 차이가 나타났다(p<0.05). 8-OHdG에서 HDT는 트레드밀 트레이닝 후에 HDS보다 낮게 나타났다(p<0.05). 해마에서 c-jun, BDNF 그리고 간에서 MDA의 단백질 발현은 HDT가 트레드밀 트레이닝 후 HDS보다 높게 나타났다(p<0.05). 결론적으로 8주간 트레드밀 훈련은 고지방식이 비만 유도 쥐의 혈청지질 성분의 불균형을 개선시키고, 조직과 혈청의 산화적 손상과 DNA 손상을 완화시켜 주어, 비만으로 인한 합병증 예방에 도움을 줄 수 있을 것으로 사료된다. 또한 NT의 발현을 증가시킴으로써 손상된 뇌기능과 신경세포의 생성 기전 활동에 긍정적 영향을 나타냄으로써 공간적 학습기능의 향상을 가져온 것으로 판단된다.

• 대한본초학회지
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• 제31권1호
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• pp.7-15
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• 2016

Objectives : Polygalae Radix (POL) has an ameliorating effect on learning and memory impairment caused by cerebral hypoperfusion. In regard to POL's action mechanism, this study was carried out to investigate the effects of POL on oxidative damage and neuronal apoptosis induced by cerebral hypoperfusion in rats.Methods : The cerebral hypoperfusion was induced by permanent bilateral common carotid artery occlusion (pBCAO) in Sprague-Dawley rats. POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in the brain tissue were measured using ELISA method. Expressions of 4-hydroxynonenal (4HNE) and 8-hydroxy-2'- deoxyguanosine (8-OHdG) were observed using immunohistochemistry. In addition, neuronal apoptosis was evaluated with Cresyl violet staining, TUNEL labeling, and immunohistochemistry against Bax and caspase-3.Results : POL treatment significantly increased SOD activities and significantly reduced MDA levels in the cerebral cortex. The up-regulations of 4HNE and 8-OHdG expression caused by pBCAO in the CA1 of hippocampus were significantly attenuated by POL treatment. POL treatment also restored the reduction of CA1 thickness and CA1 neurons caused by pBCAO and significantly attenuated the apoptotic markers including TUNEL-positive cells, Bax, and caspase-3 expression in the CA1 of hippocampus.Conclusions : The results show that POL attenuated the oxidative damage in brain tissue and neuronal apoptosis in the hippocampus caused by the cerebral hypoperfusion. It suggests that POL can be a beneficial medicinal herb to treat the brain diseases related to cerebral hypoperfusion.

• 생명과학회지
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• 제30권6호
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• pp.513-521
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• 2020

Bmi1은 PcG 단백의 일종으로 PRC를 구성하는 성분이다. Bmi1에 관한 초기의 연구는 주로 암세포에서의 역할에 집중되었고, 그 결과 Bmi1은 암세포의 증식과 생존에 중요한 역할을 하는 것으로 받아들여지고 있다. 그러나, 최근의 연구 결과 Bmi1은 퇴행성 신경계 질환이 있는 뇌에서 발현이 감소되어 있고 미토콘드리아의 기능과 활성 산소 수준을 조절하는 것으로 알려져 있다. 본 연구에서는 Bmi1 발현 저하 동물을 이용하여 간질에서 Bmi1의 약물 치료 표적 가능성을 밝히고자 하였다. Bmi1의 발현은 pilocarpine에 의한 경련중첩증 이후 해마의 CA1, CA3 그리고 치상회에서 뚜렷하게 증가하였다. 경련 양상을 볼 때 경련중첩증이 유도되는 비율은 Bmi1^+/+와 Bmi1^+/- 생쥐에서 각각 43.14%와 53.57%로 나타났다. 그러나, 치사율과 해마의 신경세포 손상에는 두 군 간에 통계적으로 유의한 차이를 보이지 않았다. 경련중첩증 유도 2개월 후에 나타난 간질 경련의 빈도수는 통계적 유의성은 없었으나 Bmi1^+/- 생쥐에서 약 50% 낮게 나타났다. 반면, 이끼섬유발아는 Bmi1^+/- 생쥐에서 통계적으로 유의하게 증가하였다. 이러한 결과를 종합하면, Bmi1의 발현이 감소할 때 pilocarpine에 의한 경련 유도와 이끼섬유발아가 증가함을 보여준다.

• 대한본초학회지
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• 제31권6호
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• pp.73-81
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• 2016

Objectives : $18{\beta}$-Glycyrrhetinic acid (18betaGA) is an metabolite of glycyrrhizin in Glycyrrhiza (licorice). The present study investigated anti-inflammatory and anti-apoptosis effect of 18betaGA on the brain tissue of lipopolysaccharide (LPS)-treated C57BL/6 mice. Methods : 18betaGA was administered orally with low (30 mg/kg) and high (100 mg/kg) doses for 3 days prior to LPS (3 mg/kg) injection. Pro-inflammatory cytokines mRNA including tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin (IL)-$1{\beta}$, IL-6, and inflammatory enzyme cyclooxygenase-2 (COX-2) mRNA were measured in the cerebral cortex, hippocampus, and hypothalamus tissue using real-time polymerase chain reaction at 24 h after the LPS injection. Histological changes of Cornu ammonis area 1 (CA1) neurons, Bax, Bcl-2, and caspase-3 expression in the hippocampus was also evaluated by immunohistochemistry and Western blotting method. Results : 18betaGA significantly attenuated the up-regulation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 mRNA, and COX-2 mRNA expression in the brain tissues induced by the LPS injection. 18betaGA also significantly attenuated the reductions of the thickness of CA1 and the number of CA1 neurons. The up-regulation of Bax protein expression in the hippocampal tissue by the LPS injection was significantly attenuated, while the ratio of Bcl-2/Bax expression was increased by 18betaGA treatment. 18betaGA also significantly attenuated the up-regulation of Bax and caspase-3 expression in the CA1 of the hippocampus. Conclusion : This results indicate that 18betaGA has anti-inflammatory and anti-apoptosis effect under neuroinflammation induced by the LPS injection and suggest that 18betaGA may be a beneficial drug for various brain diseases accompanied with the brain tissue inflammation.

• 생명과학회지
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• 제28권5호
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• pp.517-523
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• 2018

만성적 스트레스가 있는 상황에서, 과잉 생산된 cortisol은 glucocorticoid receptor (GR)를 활성화시킴으로써 해마(hippocampus)에 있는 신경 세포에 손상을 줄 수 있다. Cortisol을 생성하지 못하는 동물들의 경우, corticosterone이 스트레스 호르몬의 역할을 하는 것으로 알려져 있다. 한편, 인간의 경우, corticosterone은 aldosterone의 전구물질 이거나 cortisol과 비슷한 특성을 가지는 하나의 glucocorticoid로만 여겨져 왔다. 최근 인간을 대상으로 cortisol과 dexamethasone과 같은 합성 glucocorticoid의 기능에 관한 연구가 많이 이루어져 왔으나, corticosterone의 정확한 기능에 대하여 많이 알려져 있지 않다. 본 연구에서 corticosterone을 여러 농도로 SH-SY5Y 세포에 처리한 후 24시간과 48시간 때 viability를 조사한 결과, 높은 농도($500{\mu}M$과 $1,000{\mu}M$)에서 SH-SY5Y 세포의 성장 억제가 관찰된 반면, 낮은 농도($100{\mu}M$)에선 그 효과가 나타나지 않았다. 맥문동, 오미자, 복신 열수 추출물에 대한 세포 독성을 실시한 결과, 세 시료 모두 농도가 높아질수록 높은 세포 독성을 보였다. 한편, $500{\mu}g/ml$의 맥문동은 corticosterone에 의해 유도된 세포 성장 억제를 완화시켜 세포 성장을 회복시키는 효과를 보였다. 마지막으로, 맥문동 $500{\mu}g/ml$에 오미자와 복신의 농도를 달리하여 제조한 여러 혼합물의 시너지 효과를 알아본 결과, 대부분 혼합물이 약간의 효과를 보이긴 했으나, 음성 대조군 수준만큼 회복되지는 않았다.

• 대한감각통합치료학회지
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• 제2권1호
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• pp.21-32
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• 2004

Objective : Effect of treadmill exercise on hippocampal neural cell proliferation under normal conditions and alcohol intoxication conditions has been recently studied; however, this effect under sensory stimulation application has not clarified yet. In the present study, the effect of compression stimulation application on hippocampal neural cell proliferation in the dentate gyrus in normal and alcohol intoxicated rats was investigated. Methods : Experimental design: comparative investigation on number of 5-Bromo-2'-deoxyuridine(BrdU)B-positive cells in dentate gyrus 5 days after commencement. Setting: animal laboratory. Participants: male Sprague-Dawley rats of 3weeks old in age weighing $80{\pm}10gm$. Intervention: animals were randomly assigned into 4 groups; control-rest group(n=8), control-compression group(n=8), alcohol intoxication-rest group(n=8) and alcohol intoxication-compression group(n=8). Animals of the alcohol intoxicated groups were injected intraperitoneally with alcohol(2g/kg) twice per day for 3 days. All animals were injected BrdU(50mg/kg) intraperitoneally, and rats compression stimulation application groups were compressed using sphygmomanometer cuff times per day, for 5 days following alcohol administration. Measures: mean number of BrdU-positive cells in dentate gyrus was observed via immunohistochemistry. Results : Compression stimulation application significantly increased the number of BrdU-positive cells in the dentate gyrus. Also, treatment with alcohol for 3 days inhibited cell proliferation, and compression stimulation application alleviated alcohol-induced inhibition of new cell formation. Conclusion : These results suggest the possibility that compression stimulation application may help in improvement following alcohol-induced brain damaged.

• 동의생리병리학회지
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• 제22권4호
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• pp.771-777
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• 2008

Chungpaesagan-tang which is used for treating patients of brain in cerebrovascular disease frequently from clinical doctor has not reported about the effect of neuronal aptosis caused of brain ischemia. The aim of this study is to investigate effect of Chungpaesagan-tang protecting neuronal cells from being damaged by brain ischemia through using organotypic hippocampal slice cultures. We caused ischemic damage to organotypic hippocampal slice cultures by oxygen and glucose deprivation. And added Chungpaesagan-tang extract to cultures. thereafter we measured area percentage of propidium iodide (PI)-stained neuronal cell, lactate dehydrogenase (LDH) levels in culture media and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells. Area percentage of PI-stained neuronal cells and count of TUNEL-positive cells in CA1 and DG area of organotypic hippocampal slice culture were significantly decreased in pertinent density level of Chungpaesagan-tang extract. LDH levels in culture media of organotypic hippocampal slice culture were significantly decreased in pertinent density level of Chungpaesagan-tang extract. Within pertinent density level, Chungpaesagan-tang has cell protection effect that prevents brain ischemia damaging neuronal cells and apoptosis increasing.

• 동의생리병리학회지
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• 제17권3호
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• pp.791-797
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• 2003

This study investigated the effect of Yanggyuksanhwa-tang on cerebral ischemia of the rats. Considering age-related impact on cerebral ischemia, aged rats (18 months old) were used for this study. Ischemic damage was induced by the transient occlusion of bilateral common carotid arteries (BCAO) under the hypotension. Yanggyuksanhwa-tang was administered twice orally. Then changes of pyramidal neurons and heat shock protein 72 (HSP72) expressions in ischemic damaged hippocampus were of observed. The BCAO in aged rats led significant decrease of pyramidal neurons in CA1 hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the reduction of pyramidal neurons in CA1 hippocampus following BCAO ischemia. The BCAO in aged rats led significant increase of HSP72 expression in CA1 and mild in CA3 hippocampus. While the treatment of Yanggyuksanhwa-tang significantly attenuated the increase of HSP72 expression in CA1 hippocampus following BCAO ischemia. The extent of HSP72 expression in CA2 and DG of hippocampus was not different between the sham operated group, the BCAO ischemia control group, and the group of Yanggyuksanhwa-tang administration after BCAO ischemia. The treatment of Yanggyuksanhwa-tang significantly attenuated the increase of normalized optical density depending on HSP72 expression in CA1 hippocampus following BCAO ischemia.

• 대한수의학회지
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• 제51권3호
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• pp.185-191
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• 2011

Trimethyltin chloride (TMT) has been used as a neurotoxin for inducing brain dysfunction and neuronal death. Neuronal death in the hippocampus by TMT may generate excessive nitric oxide, but there are few studies about nitric oxide synthase enzyme involved in the synthesis of nitric oxide. The purpose of present study is to analyze the TMT toxicity in each region of rat hippocampus. To evaluate the involvement of nitric oxide, we analyzed the effects of aminoguanidine known as a selective inhibitor for inducible nitric oxide synthase on behavioral changes and the hippocampus of rat by TMT toxicity. 6-week-old male Sprague-Dawley rats were administered with a single dose of TMT (8 mg/kg b.w., i.p.) and the control group was similarly administered with distilled water. TMT + aminoguanidine-treated groups were administered with aminoguanidine (10 mg/kg or 100 mg/kg b.w., i.p.) for 3 days prior to TMT injection. The rats were sacrificed 2 days after TMT administration. In the TMT-treated group, a number of cell losses were seen in CA1, CA3 and the dentate gyrus. In the TMT + aminoguanidine-treated group, neuronal death was seen in CA1 and CA3, but reduced in the dentate gyrus compared to the TMT-treated group. Western blot analysis showed that cleaved caspase-3 expression was increased in the TMT-treated group compared to the control group. However, the expression significantly declined in the TMT + aminoguanidine-treated group. The present findings suggest that inducible nitric oxide synthase is involved in neuronal death induced by TMT.