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The Effects of Treadmill Exercise on Cognitive Performance, Brain Mitochondrial Aβ-42, Cytochrome c, SOD-1, 2 and Sirt-3 Protein Expression in Mutant (N141I) Presenilin-2 Transgenic Mice of Alzheimer's Disease

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

  • Koo, Jung-Hoon (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Eum, Hyun-Sub (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kang, Eun-Bum (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Kwon, In-Su (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Yeom, Dong-Cheol (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • An, Gil-Young (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Oh, Yoo-Sung (Department of Sport Information, Seoul City University) ;
  • Baik, Young-Soo (Department of Physical Education, Kun-Yang University) ;
  • Cho, In-Ho (Exercise Biochemistry Laboratory, Korea National Sport University) ;
  • Cho, Joon-Yong (Exercise Biochemistry Laboratory, Korea National Sport University)
  • 구정훈 (한국체육대학교 운동생화학실) ;
  • 엄현섭 (한국체육대학교 운동생화학실) ;
  • 강은범 (한국체육대학교 운동생화학실) ;
  • 권인수 (한국체육대학교 운동생화학실) ;
  • 염동철 (한국체육대학교 운동생화학실) ;
  • 안길영 (한국체육대학교 운동생화학실) ;
  • 오유성 (서울시립대학교 생활체육정보학과) ;
  • 백영수 (건양대학교 운동처방학과) ;
  • 조인호 (한국체육대학교 운동생화학실) ;
  • 조준용 (한국체육대학교 운동생화학실)
  • Received : 2010.02.02
  • Accepted : 2010.03.11
  • Published : 2010.03.30

Abstract

The purpose of this study was to investigate the effects of treadmill exercise on $A{\beta}$-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, $A{\beta}$-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 $A{\beta}$-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-l 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 $A{\beta}$-induced oxidative stress in AD.

본 연구의 목적은 PS-2 (N141I) 알츠하이머 형질전환 모델 생쥐를 대상으로 트레드밀 운동이 뇌의 세포질과 미토콘드리아의 $A{\beta}$-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 $A{\beta}$-42, cytochrome c, anti-oxidant enzymes (SOD-1, SOD-2)와 Sirt-3 단백질을 분석하였다. 먼저 트레드밀운동은 Tg 집단에서 인지능력의 개선을 나타냈으며 미토콘드리아의 $A{\beta}$-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 $A{\beta}$-42를 억제시켜 알츠하이머 질환을 개선시킬 수 있는 효과적인 방법이라고 생각된다.

Keywords

Acknowledgement

Supported by : 한국연구재단

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