트레드밀 운동이 파킨슨 유도 모델 쥐의 α-synuclein 발현과 미토콘드리아 구조적 역동성에 미치는 영향

구정훈 ( Jung-hoon Koo ) 한국운동생리학회(구 한국운동과학회) 2016 운동과학 Vol.25 No.4

PURPOSE: The purpose of this study was to investigate the effects of treadmill exercise on motor function, α-synuclein (α-syn), neuronal cell survival, mitochondrial dynamic-related proteins, and sirtuin-3 (SIRT-3) in the MPTP-induced mice model of Parkinson`s disease (PD). METHODS: Twenty four mice model of PD were divided into three groups: (1) Sham control (Sham, n=8), (2) MPTP treatment (MPTP, n=8), and (3) MPTP-Exercise (MPTP-E, n=8). MPTP-E mice group were performed to exercise on a treadmill for 8 weeks (12 m/min, 60 min/day, 5 days/week). In addition, we conducted Rota-rod test to evaluate the motor function. And then, substantia nigra (SN) was evaluated to determine whether any changes in the α-syn, neuronal cell survival, SIRT-3, mitochondrial fission, and fusion proteins. RESULTS: Treadmill exercise rescued motor deficits by reducing α-syn expression and alleviating neuronal cell death in the MPTP-induce mice model of PD. In addition, treadmill exercise increased mitochondrial fusion-related protein (Opa1, Mfn1, Mfn2) and decreased mitochondrial fission-related protein (Fis1, Drp1) possibly via activating SIRT-3 expression in the MPTP-induce mice model of PD. CONCLUSIONS: Treadmill exercise improved motor function by inhibiting neurotoxicity and improving mitochondrial dynamic via reducing α-syn expression and activating SIRT-3 expression. These results indicating that improving mitochondrial dysfunction via treadmill exercise may be potent strategy to alleviate the PD pathogenesis.

고체 로케트 노즐의 구조 및 형상 설계

정훈(Hoon Jung),구자예(Ja-Ye Koo),이수용(Soo-Yong Lee) 한국항공우주학회 1996 韓國航空宇宙學會誌 Vol.24 No.4

운동과 뇌기능: 알츠하이머 질환을 중심으로

구정훈 ( Jung Hoon Koo ),조인호 ( In Ho Cho ),조준용 ( Jun Yong Cho ) 한국체육대학교 체육과학연구소 2014 스포츠사이언스 Vol.31 No.2

알츠하이머질환은 대표적인 신경퇴행성 질환으로 노인 인구의 증가에 따라 질환자의 수가 급격하게 증가하고 있다· 현재까지 알츠하이머 질환에 나타나는 주요 특징으로는 Aβ 단백질 축적에 의한 노인성 반점과 tau 단백질의 과인산화에 의한 신경세포 내 신경섬유원 축적으로 인해 뇌신경세포 사멸과 인지기능의 저하가 나타난다· 또한 알츠하이머 질환은 인슐린 저항성과 미토콘드리아 기능이상으로 뇌의 에너지 대사의 불균형이 나타나기 때문에 결과적으로 세포내 축적되어 산화적 스트레스를 일으키는 Aβ 단백질과 과 인산화된 tau 단백질의 축적을 지연시키거나 제거하기 위한 다양한 연구들이 진행되고 있다· 최근 운동이 알츠하이머 질환을 대상으로 세포내 축적되는 독성물질을 감소시키고 뇌신경세포의 사멸 억제 및 뇌신경세포생성을 증가시켜 인지력의 개선되는 것으로 보고되었다· 뿐만 아니라 운동은 알츠하이머 질환의 뇌의 인슐린 신호전달을 증가시켜 인슐린 저항성을 개선시키고, 미토콘드리아 생합성과 관련된 단백질의 발현을 증가시켜 결과적으로 뇌의 에너지대사에 효과적인 방법으로 제시되어 운동이 뇌 신경발달에 긍정적인 영향을 미칠 것으로 보고되었다· 하지만 아직까지 알츠하이머 질환을 치료하는 기전은 대부분 약물에 의존하고 있는 실정이며 운동을 통한 알츠하이머 질환에 대한 연구가 매우 부족하기 때문에 알츠하이머 질환과 운동에 관련된 구체적인 연구가 필요하다고 생각된다· Alzheimer``s disease (AD) is a representative neurodegeneration disorder that is increasing rapidly with the prolonging life expectancy and increasing elderly population· The two major pathological hallmarks of AD are the β-amyloid (Aβ) protein and neurofibrillary tangles (NFTs) in the brain and leading to neuronal cell death and ultimately cognitive dysfunction· Also brain insulin resistance and mitochondria dysfunction may significantly contribute to the AD, indicating that inhibiting and reducing of Aβ protein and NFTs is the main targets for prevention and treatment of AD· Recently, exercise decrease the Aβ protein, NFT and neuronal cell death and increase the neurogenesis and ultimately enhancement of cognitive function in AD· Moreover, exercise increase the insulin signaling pathway- relatived protein and mitochondria biogenesis factor, indicating that exercise may be beneficial in prevention or treatment of AD· However, in AD, the most of therapies have depended primarily drugs until now and effects of exercise is very short research· Therefore, more research is necessary to prove effect of exercise on AD·

트레드밀 운동이 mutant (N141I) presenilin-2 유전자를 이식한 알츠하이머질환 모델 생쥐 뇌의 Aβ-42, cytochrome c, SOD-1, 2와 Sirt-3 단백질 발현에 미치는 영향

Jung-Hoon Koo(구정훈),Hyun-Sub Eum(엄현섭),Eun-Bum Kang(강은범),In-Su Kwon(권인수),Dong-Cheol Yeom(염동철),Gil-Young An(안길영),Yoo-Sung Oh(오유성),Young-Soo Baik(백영수),In-Ho Cho(조인호),Joon-Yong Cho(조준용) 한국생명과학회 2010 생명과학회지 Vol.20 No.3

본 연구의 목적은 PS-2 (N141I) 알츠하이머 형질전환 모델 생쥐를 대상으로 트레드밀 운동이 뇌의 세포질과 미토콘드리아의 Aβ-42, cytochrome c, SOD-1, 2 and Sirt-3 단백질 발현에 미치는 효과를 알아보는데 있다. 우선 알츠하이머 형질전환 생쥐를 Non-Tg-sedentary (n=5), Non-Tg-treadmill exercise (n=5) 집단과 Tg-sedentary (n=5), Tg-treadmill exercise (n=5) 집단으로 구분하고 트레드밀 운동을 통한 신경보호 효과를 검증하기 위해 Tg와 Non-Tg집단에 12주간 트레드밀 운동을 수행한 후 인지능력을 살펴보고 뇌의 세포질과 미토콘드리아의 Aβ-42, cytochrome c, anti-oxidant enzymes (SOD-1, SOD-2)와 Sirt-3 단백질을 분석하였다. 먼저 트레드밀운동은 Tg 집단에서 인지능력의 개선을 나타냈으며 미토콘드리아의 Aβ-42와 세포질의 cytochrome c 단백질의 감소와 항산화 효소인 SOD-1, SOD-2를 유의하게 증가시켰다. 게다가 트레드밀 운동은 모든 집단에서 Sirt-3 단백질의 발현을 증가시켰다. 따라서 트레드밀 운동은 인지능력의 향상과 세포 내 스트레스를 유발하는 Aβ-42를 억제시켜 알츠하이머 질환을 개선시킬 수 있는 효과적인 방법이라고 생각된다. The purpose of this study was to investigate the effects of treadmill exercise on Aβ-42, cytochrome c, SOD-1, 2 and Sirt-3 protein expressions in brain cytosol and mitochondria in mutant (N141I) presenilin-2 transgenic mice with Alzheimer's disease (AD). The mice were divided into four groups (Non-Tg-sedentary, n=5; Non-Tg treadmill exercise, n=5; Tg-sedentary, n=5; Tg treadmill exercise, n=5). To evaluate the neuroprotective effect of treadmill exercise, Non-Tg and Tg mice were subjected to exercise training on a treadmill for 12 wk, after which their brain cytosol and mitochondria were evaluated to determine whether any changes in the cognitive performance, Aβ-42 protein, cytochrome c protein, anti-oxidant enzymes (SOD-1, SOD-2) and Sirt-3 protein had occurred. The results indicated that treadmill exercise resulted in amelioration in cognitive deficits of Tg mice. In addition, the expressions of mitochondrial Aβ-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-1 and SOD-2 were significantly increased in response to treadmill exercise. Furthermore, treadmill exercise significantly increased the expression of Sirt-3 protein in Non-Tg and Tg mice. Taken together, these results suggest that treadmill exercise is a simple behavioral intervention which can sufficiently improve cognitive performance and inhibit Aβ-induced oxidative stress in AD.

트레드밀 운동이 알츠하이머 형질전환 생쥐 뇌의 인지기능과 미토콘드리아의 PGC-1α, cytochrome-c 발현에 미치는 영향

구정훈 ( Jung Hoon Koo ),조준용 ( Jun Yong Cho ) 한국체육대학교 체육과학연구소 2013 스포츠사이언스 Vol.30 No.2

알츠하이머질환은 초기 미토콘드리아 내 Aβ-42 단백질의 축적으로 산화적 스트레스의 증가와 함께 미토콘드리아 기능이상을 일으킨다. 따라서 본 연구의 목적은 지구성 운동을 통한 인지기능 개선과 세포사멸의 손상지표인 Cytosolic Cytochrome c수준을 확인하고 미토콘드리아 기능 및 생합성에 관련된 PGC-1α에 미치는 영향을 알아보는데 있다. NSE/PS2m 알츠하이머 형질전환 생쥐 Tg-CON (n=5), Tg-EXE (n=5) 집단과 비 형질전환 생쥐 Non-Tg-CON (n=5), Non-Tg-EXE (n=5) 집단으로 구분하고 12주간 점진적인 부하를 주어 최종 12m/min, 60min/day, 5days/weeks 강도로 트레드밀 운동을 실시하였다. 먼저지구성 운동을 통한 인지능력검사에서는 수영거리 및 시간이 Tg-CON 집단에서 유의하게 가장 높았으며 지구성 운동 후 통계적으로 유의하게 감소하여 결과적으로 알츠하이머 형질전환 생쥐의 인지력 및 행동적 능력을 향상시켰다. 세포사멸에 관련된 cyto-Cytochrome c 축적은 Tg-CON 집단에서 유의하게 가장 높았으며 Tg-EXE 집단에서는 cyto-Cytochrome c 축적이 유의하게 감소하였다. 미토콘드리아 생합성에 핵심적인 유전자인 PGC-1α는 세포질 및 미토콘드리아에서 Tg-CON 집단에서 유의한 감소 나타났으며 지구성운동 후 유의하게 증가하였다. 따라서 지구성 운동은 알츠하이머질환 초기 미토콘드리아의 기능이상을 일으키는 산화적 스트레스를 완화시키고 미토콘드리아의 생합성을 증가시켜 알츠하이머질환의 초기 예방 및 치료기전으로 효과적인 방법이라고 생각된다. Mitochondrial dysfunction and oxidative stress are early event in Alzheimer Disease``s by the accumulation of Aβ-42 in the brain mitochondria. The purpose of this study was to investgate the effects of treadmill exercise training on cognitive performance, Cytosolic Cytochorme c and mitochondria function and biogenesis factors such as PGC-1α. All mice were divided into 4 gourps (Non Tg-CON, Non Tg-exe, Tg-CON, Tg-EXE). The running speed and duration of the exercise were gradually increased and on the last week of the 12 weeks training protocol, ran 12m/min, 60m/day, 5days/week. First of all, treadmill exercise has been shown to improve cognitive and behavior function in Tg-EXE group compared with Tg-CON group. Levels of cyto-Cytochrome c in Tg-CON group were very significantly higher than all other groups, whereas treadmill exercise training decreased the expression of cyto-Cytochrome c in Tg-EXE group. In addition, level of mt-PGC-1α and cyto-PGC-1α in Tg-CON group were very significantly lower than all other groups, whereas treadmill exercise significantly enhanced the expression of mt-PGC-1α and cyto-PGC-1α in Tg-EXE group. Taken together, these finding suggest that treadmill exercise training in Tg mice alliviated the cognitive performance and up-regulation of mitochondria biogenesis in the AD brain is the main targets for prevention and treatment.

트레드밀 지구성 운동이 알츠하이머 형질전환 생쥐 뇌의 Mitochondrial Dynamic과 신경세포생존에 미치는 영향

구정훈 ( Jung Hoon Koo ),조인호 ( In Ho Cho ) 한국운동생리학회 2016 운동과학 Vol.25 No.1

PURPOSE: The aim of this study was to investigate effects of treadmill exercise on mitochondrial beta-amyloid protein, mitochondrial dynamic function and neuronal cell survival of brain cortex mitochondria in transgenic mice model with Alzheimer’s disease METHODS: Fifteen transgenic mice with Alzheimer’s disease were divided into three groups: (1) Non transgenic control (NTC, n=5), (2) transgenic control (TC, n=5) and (3) ransgenic-exercise (TE, n=5). TE mice group was subjected to treadmill exercise on a treadmill for 12 weeks (15 m/min, 60 min/day, 5 day/week), And brain cortex mitochondria were evaluated to determine any changes in the A-42, neuronal cell survival-related proteins, Sirt-3, SOD-2, and mitochondrial dynamic-related proteins. RESULTS: Treadmill exercise decreased A-42 and mitochondiral fission proteins (Drp 1, Fis 1) in the brain cortex mitochondria while it increased Sirt-3, SOD-2 and mitochondrial fusion proteins (Mfn 1, Mfn 2, Opa 1) and neuronal cell survival factors (Bcl-2/Bax ratio, mito-cytochrome c/cyto-cytochrome c ratio). Moreover, treadmill exercise improved spatial learning and cognitive function in TE group. CONCLUSIONS: Treadmill exercise protects against Aβ-induced imbalance of mitochondrial dynamic function and neuronal cell death through decreasing Aβprotein and mitochondria fission and activating mitochondrial fusion, indicating that treadmill exercise may play a role in a preventive strategy for AD-related mitochondrial dysfunction.

그룹운동 프로그램이 여자 청소년들의 체력과 정신신경면역계에 미치는 영향

변정은(Byun Jung Eun),구정훈(Koo Jung Hoon) 한국발육발달학회 2018 한국발육발달학회지 Vol.26 No.4

The purpose of this study was to investigate the effects of group exercise on physical fitness and psychoneuroimmunological factors in female adolescents. Thirty-three female adolescents were divided into three groups, control (CON; n = 11), running exercise (RE; n = 11), and group exercise (GX; n = 11) for 12 weeks of the exercise intervention. For all subjects, measurements of body composition, cardiovascular function, psychological factors, and serum neuroimmunological factors were completed before and after the 12-week intervention. First, the changes in mental stress were significantly lower in RE and GX compared with the CON group, and it was significantly decreased following the exercise intervention in RE and GX groups. Although there was no significant difference in the level of change between groups in depression and self-confidence, it was only reduced following GX intervention in GX group. The changes in peak oxygen uptake and exercise time were significantly greater in the RE and GX compared to the CON group, and it was increased after exercise intervention in RE and GX groups. The changes in percentage of body fat(BF%) were significantly lower in the GX compared to the CON group. The changes in lean body mass(LBM) were significantly greater in RE and GX compared to the CON group. Moreover, BF% was decreased whereas LBM was increased in the GX group after the exercise intervention. Finally, the changes in tumor necrosis factor alpha were only reduced in the RE group, resulting in significantly lower changes compared with CON and GX groups. More interestingly, although no significant differences were found between groups, brain-derived neurotrophic factor(BDNF) was increased following the exercise intervention in the GX group only. These findings demonstrate that GX will result in decreased BF% and increased LBM, and cardiovascular function. In addition, GX significantly decreases stress, and depression, but increases self-confidence and BDNF. Collectively, this indicates that 12 weeks of GX intervention can have a positive effect on body composition, physical fitness, and neurological function, which may contribute to improvements in psychological factors in female adolescents.

성인에서 진단된 선천성 낭포성 유선종 폐기형 6예

박영진 ( Young Jin Park ),정훈 ( Hoon Jung ),박이내 ( I Nae Park ),최상봉 ( Sang Bong Choi ),허진원 ( Jin Won Hur ),이혁표 ( Hyuk Pyo Lee ),염호기 ( Ho Kee Yum ),최수전 ( Soo Jeon Choi ),구호석 ( Ho Seok Koo ),이양행 ( Yang Haeng 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.65 No.2

연구배경: CCAM은 드문 하부 호흡기의 선천성 발달 기형으로 대부분은 생후 2년 내에 진단되는 것으로 보고되고 있다. 그리고 매우 드물게 성인이 되어서 호흡기 합병증이 생기거나 무증상인 채로 우연히 진단된 증례들이 보고되었다. 우리는 본원에서 수술을 통해 조직학적 소견으로 확진된 6명의 성인 CCAM 환자들을 기술하였고 이들의 임상적, 방사선학적 및 조직학적 특성을 분석하고자 하였다. 방법: 2001년 8월부터 2007년 2월까지 본원에서 성인기에 수술을 통한 조직학적 소견으로 확진된 6명의 CCAM 환자를 확인하였다. 의무기록 검토를 통해 그들의 인구학적 및 임상적 특성, 흉부 방사선 자료 그리고 조직학적 특성을 후향적으로 분석하였다. 결과: 6명의 CCAM 환자 중 4명이 여자였고 진단 당시의 평균 나이는 23.5세(범위 18∼39세)였다. 내원 당시 주요 임상 양상은 하부 호흡기 감염, 객혈, 그리고 기흉이었다. 흉부 전산화 단층촬영을 보면 5명의 환자는 공기 액체층을 동반한 다발성 격막을 가진 낭종성 병변을 가지고 있었고 나머지 1명에서는 우상엽에 공기 액체층을 동반한 다발성 공동성 병변과 주위에 다발성 침윤성 병변을 가지고 있었다. 모든 환자는 폐엽 절제 수술을 받았는데 5명은 개흉술을 통한 폐엽 절제술을 그리고 1명은 흉강경을 이용한 폐엽 절제술을 시행 받았다. 조직학적 검사결과 Stocker씨 분류법에 따라 3명의 환자는 1형 그리고 나머지 3명은 2형으로 분류되었다. 모든 환자의 검체에서 동반된 악성 종양의 증거는 없었다. 결론: CCAM이 하부 호흡기 감염, 기흉, 객혈 등의 다양한 호흡기 합병증과 악성화를 일으킬 가능성이 있고 수술적 치료와 연관된 합병증이 거의 없기 때문에 CCAM으로 의심되거나 확실치 않은 폐의 낭종성 혹은 공동성 병변이 있을 때 정확한 진단과 적절한 치료를 위해서 반드시 수술적 치료가 필요하다. Background: Congenital cystic adenomatoid malformation of the lung (CCAM) is a rare congenital developmental anomaly of the lower respiratory tract. Most cases are diagnosed within the first 2 years of life, so adult presentation of CCAM is rare. We describe here six adult cases of CCAM and the patients underwent surgical resection, and all these patients were seen during a five and a half year period. The purpose of this study was to analyze the clinical, radiological and histological characteristics of adult patients with CCAM. Methods: Through medical records analysis, we retrospectively reviewed the clinical characteristics, the chest pictures (X-ray and CT) and the histological characteristics. Results: Four patients were women and the mean age at diagnosis was 23.5 years (range: 18∼39 years). The major clinical presentations were lower respiratory tract infection, hemoptysis and pneumothorax. According to the chest CT scan, 5 patients had multiseptated cystic lesions with air fluid levels and one patient had multiple cavitary lesions with air fluid levels, and these lesions were surrounded by poorly defined opacities at the right upper lobe. All the patients were treated with surgical resection. 5 patients underwent open lobectomy and one patient underwent VATS lobectomy. On the pathological examination, 3 were found to be CCAM type I and 3 patients were CCAM type II, according to Stocker`s classification. There was no associated malignancy on the histological studies of the surgical specimens. Conclusion: As CCAM can cause various respiratory complications and malignant changes, and the risks associated with surgery are extremely low, those patients who are suspected of having or who are diagnosed with CCAM should go through surgical treatment for making the correct diagnosis and administering appropriate treatment. (Tuberc Respir Dis 2008;65:110-115)

한 대학병원에서 조사된 재택산소요법을 받고 있는 환자의 특성과 재택산소요법 처방에 대한 순응도: 건강보험급여전환 후 조사

구호석 ( Ho Seok Koo ),송영진 ( Young Jin Song ),이승헌 ( Seung Heon Lee ),이영민 ( Young Min Lee ),김현국 ( Hyun Gook Kim ),박이내 ( I Nae Park ),정훈 ( Hoon Jung ),최상봉 ( Sang Bong Choi ),이성순 ( Sung Soon Lee ),허진원 ( Jin 대한결핵 및 호흡기학회 2009 Tuberculosis and Respiratory Diseases Vol.66 No.3

트레드밀 운동이 고지방식이를 섭취한 비만 쥐 골격근의소포체 스트레스에 미치는 영향

홍석민 ( Seok Min Hong ),구정훈 ( Jung Hoon Koo ),권인수 ( In Su Kwon ),장용철 ( Yong Chul Jang ),강은범 ( Eun Bum Kang ),엄현섭 ( Hyun Sub Um ),이창국 ( Chang Gook Lee ),오상훈 ( Sang Hoon Oh ),권만근 ( Man Geun Kwon ),조인호 ( I 한국스포츠정책과학원(구 한국스포츠개발원) 2014 체육과학연구 Vol.25 No.3

본 연구는 고지방식이로 유도된 비만 흰쥐를 대상으로 지구성 운동이 체중변화, 글루코스 내성 및 소포체 스트레스(ER-stress)에 반응에 관여하는 단백질 발현에 미치는 영향을 규명하는데 목적이 있다. 실험동물은 16주간 고지방식이를 먹인 흰쥐를 사용하였으며 집단은 Sprague-Dawley Control(SD-Con/n=4)집단, High Fat Control(HF-Con/n=4)집단, High Fat exercise(HF-Exe/n=4)으로 구분하고 트레드밀 운동을 하루 30분, 주 5회 총 8주간 21m/min의 속도로 실시하였다. 먼저, 체중과 글루코스 내성은 HF-Con 집단에서 유의하게 가장 높았지만 트레드밀 운동을 실시한 HF-Exe집단에서 유의한 감소를 나타났다. 또한 소포체 스트레스에 반응에 관여하는 glucose-regulated protein 78 (BiP/GRP78), activating transcription factor 6 (ATF6), Pancreatic ER kinase(PERK) 및 inositol-requiring 1α (IRE-1α)/X-box binding protein 1 (XBP-1)은 HF-Con 집단에서 유의하게 증가를 나타냈고, HF-Exe 집단에서 유의한 감소가 나타났다. 따라서 지구성 운동은 고지방 식이로 유도된 비만 휜쥐의 체중 감소와 글루코스 내성을 개선시키고, 소포체 스트레스를 감소시키는데 긍정적인 영향을 미치는 것으로 생각된다. This study was to performed to the effect of 8-week endurance exercise influences on body weight, glucose tolerance and ER-stress in soleus of 16weeks Rats fed High-Fat diet. Rats were randomly assigned to 3 group; (1)Sprague-Dawley Control diet (SD-Con/n=4), (2)High-Fat diet Control (HF-Con/n=4), (3)High-Fat diet Exercise (HF-Exe/n=4). Exercise group ran on the treadmill for 30min/day at the level of 21m/min for 5days/week during 8weeks. Results showed that body weight and glucose tolerance of the HF-Con group was remarkably increased(p<.05) compared to other groups. However, HF-Exe group significantly decreased body weight and glucose tolerance compared to HF-Con group. Moreover, level of GRP78, ATF6, PERK and IER1?, which are main proteins of ER-stress were significantly increased in HF-Con group higher than other group, whereas HF-Exe group significantly decreased the expression of GRP78, ATF6, PERK and IER1?. Taken together, these finding suggested that the reduction of the body weight, glucose tolerance and unfolded protein response by treadmill exercise may represent a positive adaptation protecting against high-fat diet-induced ER stress.