트레드밀 운동이 ICV-STZ 처치 흰쥐의 뇌 인슐린 신호전달, 포도당 대사 및 Tau 단백질 과인산화에 미치는 영향

강은범 ( Eun Bum Kang ),김창환 ( Chang Hwan Kim ),조준용 ( Joon Yong Cho ) 한국운동생리학회(구 한국운동과학회) 2014 운동과학 Vol.23 No.2

본 연구의 목적은 intracerebroventricular(ICV)에 streptozotocin(STZ) 처치로 유도된 알츠하이머 치매 흰쥐를 대상으로 6주간의 트레드밀 운동이 brain insulin signaling, 포도당 대사 및 Tau 단백질 과인산화에 미치는 영향을 규명하는 것이다. 알츠하이머 질환 동물 모델을 만들기 위해 20주령의 Sprague-Dawley 흰쥐의 양쪽 대뇌 뇌실에 STZ(1.5mg/kg)를 주입하였다. 이들 실험동물은 ICV-Sham(n=6), ICV-STZ CON(n=6), ICV-STZ TE(n=6)로 구분하였다. 트레드밀 운동은 하루에 30분, 주5일, 6주간 실시하였다. 트레드밀 운동 실시 전과 후에 수중미로검사(Water Maze Test)를 실시하였다. ICV-STZ CON 그룹은 ICV-Sham 그룹에 비해 탈출시간과 탈출거리가 유의하게 증가된 것으로 나타났다. 하지만 6주간 트레드밀 운동을 실시한 ICV-STZ TE 집단은 ICV-STZ CON 그룹에 비해 탈출시간과 탈출거리가 유의하게 감소된 것으로 나타났다. ICV-STZ CON 그룹의 대뇌 해마에서 Tau 단백질의 과인산화가 증가하고 brain insulin signaling의 활성이 감소된 것으로 나타났다. 하지만 트레드밀 운동을 실시한 ICV-STZ TE 집단에서 Tau 단백질의 과인산화가 ICV-STZ CON 그룹에 비해 감소된 것으로 나타났으며 brain insulin signaling 관련 단백질(IR, PI3K, AKT)의 활성은 증가된 것으로 나타났다. 또한 Tau 단백질의 주요 kinase인 GSK3β의 인산화는 증가하여 활성이 감소됨을 확인할 수 있었다. 뇌 포도당 수송체인 GLUT1과 GLUT3은 해마에서 모두 발현이 감소되었지만 트레드밀 운동을 통해 포도당 이용효율이 높아진 것으로 나타났다. 이상의 결과를 종합하면 트레드밀 운동을 통해 neurofibrillary tangle의 구성요소인 Tau 단백질의 과인산화가 억제되었으며 인지능력이 개선되는 효과를 가져왔다. 즉 신체활동과 같은 유산소 운동은 알츠하이머 질환의 예방과 치료에 효과적인 대안으로 적용될 수 있음을 의미한다. The purpose of this study was to explore the effect of 6-week treadmill exercise on brain insulin signaling, glucose metabolism and hyperphosphorylation of Tau protein in Alzheimer dementia rats induced by intracerebroventricular (ICV) treatment of streptozotocin (STZ). To produce Alzheimer animal model, STZ (1.5 mg/kg) was injected in both cerebral ventricles of 20-week Sprague-Dawley rats, which were classified into ICV-Sham, ICV-STZ CON and ICV-STZ TE (treadmill exercise). Treadmill exercises were conducted for 3 0 minutes a d ay, 5 days a w eek and for the duration of 6 weeks. Water maze tests were performed before and after the treadmill exercises. Time and distance of escape significantly increased in ICV-STZ CON group compared with those in ICV-Sham group. Nevertheless, time and distance of escape significantly decreased in ICV-STZ TE group with 6-week treadmill exercise compared with those in ICV-STZ CON group. The treatment of ICV-STZ increased hyper phosphorylation of Tau protein and decreased the activity of brain insulin signaling in cerebral hippocampus of rats. Yet, hyperphosphorylation of Tau protein decreased more in I CV-STZ TE group, for which treadmill exercise were administered, than in I CV-STZ C ON group while the activity of proteins related to brain insulin signaling (IR, PI3K, AKT) increased. In addition, phosphorylation of GSK3, a major kinase of Tau protein, increased which resulted in the decrease of activity. Although both GLUT1 and GLUT3, glucose transporters in brain, decreased expression in hippocampus, treadmill exercise increased utilization efficiency of glucose in the brain. Treadmill exercise suppressed hyperphosphorylation of Tau protein, a component of neurofibrillary tangle, and resulted in the enhancement of perceptive ability. In conclusion, aerobic exercise can be administered as an effective alternative in the prevention and treatment of Alzheimer`s disease.

트레드밀 운동이 알츠하이머 형질전환 동물의 인지능력 및 신경영양성인자에 미치는 영향

강은범 ( Eun Bum Kang ),육현철 ( Hyun Chul Youk ) 한국체육대학교 체육과학연구소 2012 스포츠사이언스 Vol.30 No.1

The purpose of this study was to investigate the effects of treadmill exercise on cognitive function and neurotrophic factor using transgenic animal model of Alzheimer’s disease(NSE/APP695sw mouse, NSE/hTau23 mouse). Subjects were divided into APP-CON (APP Control group, n=4), APP-EXE (APP Exercise group, n=4), Tau-CON (Tau Control group, n=4) and Tau-EXE (Tau Exercise group, n=4). Treadmill exercise was conducted for 12 weeks (20 cm/sec, 30 min, 3 wk; 22 cm/sec, 35 min, 3 wk; 22 cm/sec, 45 min, 3 wk; and 24 cm/sec, 50 min, 3 wk). Water Maze Test was conducted to investigate the improvement of`` cognitive ability through 12 weeks of treadmill exercise. Both NSE/APPsw transgenic mice and NSE/htau23 transgenic mice having performed treadmill exercise were found to show a statistically significant reduction in the swimming time (p=.001) and the swimming distance (p=.001). However, there was no significant difference found in the swimming speed. As a result, this study found out that treadmill exercise helped improve the cognitive ability of Alzheimer``s disease transgenic mice. Besides, through Western blot experiment, this study confirmed BDNF and NGF proteins that are neurotrophic factors. In the brain of NSE/APPsw transgenic mice and NSE/htau23 transgenic mice having performed treadmill exercise, it was found that the expression of BDNF and NGF proteins increased. Through an increase of the expression of BDNF (p=.001) and NGF (p=.001) proteins that are neurotrophic factors, this styd found out that the growth and survival of neurons increased as well. This study results indicated that regular exercise may be applied as preventive and therapeutic methods, which may positively improve Alzheimer``s disease.

트레드밀 운동이 streptozotocin 뇌실 처치로 유발된 알츠하이머 동물 모델 쥐의 신경염증과 신경세포사멸에 미치는 영향

강은범 ( Eun Bum Kang ) 한국스포츠정책과학원(구 한국스포츠개발원) 2015 체육과학연구 Vol.26 No.1

본 연구는 뇌실(intracerebroventricular; ICV)에 streptozotocin(STZ) 처치로 유도된 알츠하이머 동물 모델 쥐를 대상으로 6주간의 트레드밀 운동이 별아교세포(astrocyte)에서의 염증반응, 해마 부위에서 염증관련 단백질과 신경세포의 사멸에 미치는 영향을 알아보았다. 실험동물은 Sham-CON(n=10), ICV-STZ CON(n=10), ICV-STZ TE(n=10)로 구분하였다. 트레드밀 운동은 하루에 30분, 주5일, 6주간 실시하였다. 먼저 수중미로검사에서 ICV-STZ CON 집단은 Sham-CON 집단에 비해 원형도피대를 찾는 시간과 거리가 유의하게 증가된 것으로 나타났다. 하지만 트레드밀 운동을 실시한 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 원형도피대를 찾는 시간과 거리가 유의하게 감소된 것으로 나타났다. 별아교세포의 marker인 신경아교원섬유성산성단백질(glial fibrillary acidic protein; GFAP)의 경우 ICV-STZ CON 집단은 Sham-COM 집단에 비해 발현이 증가되었지만 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 감소된 것으로 나타났다. 염증반응과 관련해서 ICV-STZ CON 집단은 Sham-CON 집단에 비해 TNF-α, IL-1β, Lipocalin-2, COX-2의 발현이 증가한 것으로 나타났지만 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 감소된 것으로 나타났다. 신경세포의 사멸과 관련해서 ICV-STZ CON 집단은 Sham-CON 집단에 비해 caspase-3 와 Bax의 발현이 증가하였지만, Bcl-2는 감소한 것으로 나타나 신경세포의 사멸이 증가하는 것으로 나타났다. 하지만, 트레드밀 운동을 실시한 ICV-STZ TE 집단은 ICV-STZ CON 집단에 비해 신경세포의 사멸이 감소하는 것으로 나타났다. 따라서 본 연구에서 실시한 트레드밀 운동은 알츠하이머 동물 모델 쥐의 인지능력 저하의 개선, 염증반응의 감소 그리고 신경세포의 사멸을 억제하는 긍정적인 효과가 있는 것으로 나타났다. 즉 트레드밀 운동과 같은 유산소 운동은 알츠하이머 질환의 증상을 개선하기 위한 효과적인 대안으로 적용될 수 있다. The purpose of this study was to explore the effects of 6-week treadmill exercise on inflammation and neuronal cell death in the hippocampus of intracerebroventricular (ICV) streptozotocin (STZ)-injected Alzheimer``s disease (AD) rats. The experimental animals were divided into Sham-CON group (n=10), ICV-STZ CON group (n=10) and ICV-STZ TE group (n=10). The treadmill exercise was conducted for 30 minutes a day, 5 days a week, for 6 weeks. First, in a water maze test, it turned out that the time and distance of finding an escape platform significantly increased in the ICV-STZ CON group as compared to those in the Sham-CON group. In contrast, it turned out that the time and distance of finding the escape platform significantly decreased in the ICV-STZ TE group in which the treadmill exercise was carried out as compared to those in the ICV-STZ CON group. The expression of marker of astrocytes, Glial Fibrillary Acidic Protein (GFAP) increased in the ICV-STZ CON group as compared to that in the Sham-COM group, but that in the ICV-STZ TE group decreased as compared to that in the ICV-STZ CON group. Regarding inflammatory reactions, it turned out that the expressions of TNF-α, IL-1β, Lipocalin-2 and COX-2 increased in the ICV-STZ CON group as compared to those of the Sham-CON group, but it turned out that those of the ICV-STZ TE group decreased as compared to those of the ICV-STZ CON group. Regarding neuronal cell deaths, the expressions of caspase-3 and Bax increased in the ICV-STZ CON group as compared to the Sham-CON group, but it turned out that the expression of Bcl-2 decreased, and the neuronal cell deaths increased. However, it turned out that the neuronal cell deaths decreased in the ICV-STZ TE group in which the treadmill exercise was carried out as compared to that in the ICV-STZ CON group. Therefore, it turned out that the treadmill exercise showed positive effects on improving cognitive ability by reducing inflammatory reactions and inhibiting neuronal cell deaths in the rats with AD. In other words, aerobic exercise like treadmill exercise can be applied as an effective alternative to improve symptoms of AD.

트레드밀 운동이 D-galactose로 유도된 노화 쥐의 골격근에서 미토콘드리아의 구조적 역동성에 미치는 효과

강은범 ( Kang Eun-bum ),조준용 ( Cho Joon-yong ) 한국체육대학교 체육과학연구소 2021 스포츠사이언스 Vol.39 No.1

The purpose of this study was to investigate the effects of treadmill exercise on mitochondrial dynamic-related proteins in skeletal muscle of D-galactose-induced aging rats. Aging was induced using D-galactose treatment, and experimental groups were divided into a sham control (SC; n=7), a aging control (AC; n=7) and a aging exercise (AE; n=7) group. The rats were subsequently subjected to treadmill exercise (progressively increasing load intensity) for 8 weeks (5 min 8 m/min, the 5 min 11 m/min, final 20 min 14 m/min). The rats were subsequently subjected to treadmill exercise (progressively increasing load intensity) for 8 weeks. Mitochondrial homeostasis in the skeletal muscle through treadmill exercise was confirmed by the western blot experiment to confirm the expression of mitochondrial dynamism-related proteins. Through treadmill exercise treatment, the expression of mitochondrial cleavage-related proteins (Drp1. Fis1) in the skeletal muscle of the AE group was decreased, and the expression of Mfn1 and Opa1 among the fusion-related proteins was increased. However, the Mfn2 protein did not show any difference. In conclusion, treadmill exercise is thought to have the effect of improving mitochondrial dynamics that regulates the quantity and quality of mitochondria by positively regulating the fusion and division processes for regulating mitochondrial homeostasis in skeletal muscle. Therefore, it is believed that physical activities such as treadmill exercise can effectively prevent mitochondrial deterioration in skeletal muscle that may occur during aging.

트레드밀 운동이 고지방 식이 쥐 심근세포의 미토콘드리아 역동성에 미치는 영향

강은범 ( Eun-bum Kang ),조준용 ( Joon-yong Cho ) 한국체육대학교 체육과학연구소 2021 스포츠사이언스 Vol.39 No.3

Mitochondria that produce energy to keep the function of the heart normal play a very important role. Obesity is known to be indirectly linked to various heart diseases. This study would check if the improvement of obesity through physical activities could improve the abnormal mitochondrial dynamics in cardiac muscles. For experimental animals, obesity was induced through a long-term high-fat diet (20 weeks). The groups were divided into ND-CON (n=7), HFD-CON (n=7), and HFD-TE (n=7) groups. Treadmill exercise was conducted 5 days a week, for 8 weeks. Regarding mitochondrial homeostasis in the cardiac muscles through treadmill exercise, mitochondrial dynamics- related protein expression was checked, using a Western blot test. First, for factors related to mitochondrial fusion-related factors, including Mfn1, Mfn2, and Opa1, there was a statistically significant decrease in protein expression in the HFD-CON group than in the ND-CON group. In contrast, there was a statistically significant increase in protein expression in the HFD-TE group than in the HFD-CON group. In addition, as for mitochondrial fusion-related factors, including Drp1 and Fis1, protein expression increased in the HFD-CON group than in the ND-CON group while it decreased in the HFD-TE group than in the HFD-CON group. In conclusion, obesity abnormally induces mitochondrial fusion and fission in the cardiac muscles; however, it turned out that this pathological phenomenon is improved by treadmill exercise. As a result, it is judged that it affected the positive regulation of mitochondrial dynamics. Thus, it is judged that physical activities like treadmill exercise can effectively prevent the decreased heart function induced by obesity.

트레드밀 운동이 고지방 식이 쥐의 해마에서의 소포체 스트레스와 인슐린 저항성에 미치는 영향

강은범 ( Eun Bum Kang ) 한국운동생리학회 2015 운동과학 Vol.24 No.2

PURPOSE: The purpose of this study was to investigate the impacts of 8-week treadmill exercise on glucose metabolism, insulin resistance and ER stress-related factors in hippocampal tissue with experimental animals for which obesity was induced through 20-week high-fat diet. METHODS: 20-week-old SD rats was provided high-fat diet for 20 weeks for inducing obesity. The experimental animals were divided into a Normal Diet Control Group (ND-CON, n=6), a High-Fat Diet Control Group (HFD-CON, n=6) and, a High-Fat Diet Exercise Group (HFD-EXE, n=6). The treadmill exercise was conducted, 30 minutes a day, four days a week for eight weeks. After the treadmill exercise, their weight, AUC and HOMA-IR were analyzed. ER stress-related variables (GRP78/BiP, PERK, ATF6, IRE1 , eIF2, XBP-1S α α & CHOP) were analyzed using the Western blot method. RESULTS: The body weight, HOMA-IR, and expression of ER stress-related variables increased while blood glucose disposal capacity decreased in HFD-CON. However, the body weight, HOMA-IR, and ER stress-related variables decreased while blood glucose disposal capacity improved in HFD-EXE than HFD-CON. CONCLUSIONS: It was found that aerobic exercise would play positive roles in improving the imbalanced energy metabolism induced by obesity and controlling ER stress to protect against hippocampal tissue damage.

복합 트레이닝 프로그램이 조정선수들의 심폐기능 및 혈중 젖산농도에 미치는 영향

허정은 ( Jung Eun Her ),강동균 ( Dong Kyun Kang ),변원태 ( Won Tae Byun ),강은범 ( Eun Bum Kang ),조인호 ( In Ho Cho ) 한국체육대학교 체육과학연구소 2013 스포츠사이언스 Vol.31 No.1

The purpose of this study is to examine combined training effect on physiological factors and athletic performance ability in 2000m indoor rowing athletes. Well-trained rowing athletes were participated in this study (age 20.24±0.29 yrs; height 184.40±1.20 cm; exercise carreer 5.07±0.44 yrs, BMI: 22.40±0.46, WHR 0.80±0.01)and 8-week combined training were performed. Combined training included weight training (Lat puldown, Shoulder press, Wrist curl, Squat, Dumbbell lunge, Leg curl) and indoor rowing machine with 60-second maximal stroke exercise with gradually increased exercise intensity. Blood lactate concentration after training did not differ according to the method of training.. For heart rate, there was no difference in each 500m section with and without training and there was a statistical difference in 500, 1000, and 2000m section based upon combined training. Each 500m rowing section time was statistically decreased due to combined training however, there was no difference in stroke rate. In conclusion, combined training may increase aerobic and anaerobic power ability, and there fore, this may positively affect athletic performance ability.

초등학생의 손가락 길이 비율(2D:4D ratio)에 따른 체격 및 체력요인 비교

송영은 ( Young-eun Song ),강은범 ( Eun-bum Kang ),김창환 ( Chang-hwan Kim ) 한국운동생리학회(구 한국운동과학회) 2016 운동과학 Vol.25 No.3

PURPOSE: The purpose of this study is to investigate if the second to fourth finger length ratio (2D:4D ratio) can be used as a factor to predict elementary student`s athletic ability. METHODS: With the participation of 371 elementary students (223 male, 148 female), X-ray images of their hands were taken for the analysis of the length from the midpoint between the distal end of the metacarpal bone and the proximal end of the proximal phalanges to the tip of the finger. As for group classification, students were divided into three groups: Low group for those less than 25%; Medium group for those between 25 and 75%; and High group for those above 75%. RESULTS: It was found that 2D:4D ratio of male students were statistically significantly lower than that of female students. As for physique factors according to 2D:4D ratio by grade and gender, statistically significant difference was found in the height of fourth grade female students. Among other groups, no other items indicated difference in physique factor. In addition, as for physical factors, statistically significant difference was not found in any group or item. Lastly, it was found that there is no correlation between 2D:4D ratio and physical factors. CONCLUSIONS: In conclusion, 2D:4D was found of which reliability was low as predictors of elementary student`s physique and physical fitness factors. Consequently, it is considered that further studies will be required for whether the innate 2D:4D ratio and sex hormone can be changed through longitudinal study.

지구성 운동이 NSE/APPsw 알츠하이머 질환 생쥐의 인지능력, Aβ-42, BDNF, GLUT-1과 HSP-70 단백질 발현에 미치는 영향

엄현섭(Hyun-Sub Eum),강은범(Eun-Bum Kang),임예현(Yea-Hyun Lim),이종록(Jong-Rok Lee),조인호(In-Ho Cho),김영수(Young-Soo Kim),채갑룡(Kab-Ryoung Chae),황대연(Dae-Yean Hwang),곽이섭(Yi-Sub Kwak),오유성(Yoo-Sung Oh),조준용(Joon-Yong Cho) 한국생명과학회 2008 생명과학회지 Vol.18 No.6

알츠하이머 질환은 신경퇴행성질환으로 노령인구에서 뿐만 아니라 30~60세 사이에서도 상염색체성우성형으로 발생하여 사회문제로 대두되고 있으며 발병기전도 명확하게 규명되지 않은 상태이다. 따라서 이 연구에서는 hAPP695sw 돌연변이를 neuron-specific enolase (NSE) 유전자의 프로모터 조절 하에 연결시킨 융합 유전자(pNSE/APP695sw fu-sion gene)를 과 발현시킨 알츠하이머 질환 모델생쥐를 대상으로 16주간 지구성 운동에 따른 알츠하이머 질환 모델생쥐의 인지능력의 변화와 주병변인 Aβ-42 단백질과 함께 GLUT-1, BDNF, HSP-70 단백질의 발현량을 분석하였다. 그 결과 지구성 운동은 APPsw 알츠하이머 질환 모델생쥐의 인지능력을 개선시키는데 긍정적인 영향을 미친 것으로 나타났으며 이러한 인지능력의 개선은 알츠하이머 질환의 주 병변인 뇌의 Aβ-42 감소뿐만 아니라 BDNF, GLUT-1과 HSP-70 단백질의 발현 증가와 관련이 있음을 확인하였다. 따라서 지구성 운동은 약물 처치 이외에 알츠하이머 질환을 예방하거나 지연시킬 수 있는 전략적인 방법으로 활용할 수 있음을 알 수 있다. Mutations in the APP gene lead to enhanced cleavage by β- and γ-secretase, and increased Aβ formation, which are closely associated with Alzheimer’s disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes (Aβ-42, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer’s disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer’s brains. Sixteen weeks of exercise training resulted in a reduction of Aβ-42 peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of Aβ-42 peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer’s disease.

그룹운동 프로그램의 참여중지가 여자 청소년의 신체구성, 심폐체력 그리고 정신신경면역계에 미치는 영향

변정은 ( Byun Jung-eun ),구정훈 ( Gu Jung-hoon ),강은범 ( Kang Eun-bum ) 한국체육대학교 체육과학연구소 2019 스포츠사이언스 Vol.36 No.2

The purpose of this study was to investigate the effects of group exercise and detraining on body composition, cardiorespiratory 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) and these were used for the analysis. For all subjects, measurements of body composition, cardiorespiratory fitness, psychoneuroimmunological factors, and serum neuroimmunological factors were completed before and after detraining. First, the changes in maximal oxygen uptake and exercise duration were significantly lower in RE and GX compared with the CON group, and it was significantly decreased after detraining than before detraining, but maximum heart rate was no significant difference in the level of change between groups. The change of serum n BDNF was significantly lower in RE and GX compared with the CON group, but IL-6, MCP-1, TNF-α were no significant difference in the level of change between groups. Finally, body composition(body weight, percentage of body fat, BMI) and mental stress(stress, depression and self-confidence) were no significant difference in the level of change between groups. Collectively, this indicates that 4 weeks of detraining can have negative effect on the cardiorespiratory fitness and BDNF in female adolescents. If more specific studies were conducted according to the participation period and detraining period of the exercise program, the most appropriate exercise duration period and the period of detraining will be revealed which may contribute to be provide the optimal exercise program effective for physical health and psychoneuroimmunological for the female adolescents.