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트레드밀 운동이 알츠하이머 질환의 미토콘드리아 항상성 기전에 미치는 영향

Ameliorative effect of treadmill exercise on cognitive deficits and amyloid-b pathology through the mitophagy in a mouse model of Alzheimer's disease

조준용|엄현섭|권기천|최동훈|오은택
국민체육진흥공단 한국스포츠과학원 (Korea Institute of Sport Science)|2020.12|체육과학연구 (Korean Journal of Sport Science)|제31권 제4호|pp. 612-625|DOI 10.24985/kjss.2020.31.4.612

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참고문헌

키워드

cognitive function인지기능apoptosis아밀로이드mitochondrial biogenesis세포사멸amyloid미토파지미토콘드리아 생합성mitophagy
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초록

[목적] 본 연구는 알츠하이머(alzheimer's disease: AD) 형질전환 생쥐를 대상으로 12주간의 트레드밀 운동이 미토콘드리아 항상성 기전에 미치는 영향을 확인하기 위해 미토파지와 미토콘드리아 생합성 관련 단백질을 분석하여 이를 통해 Aβ 감소와 인지기능이 개선되는지 확인하는데 있다. [방법] 실험동물은 non-tg-control(NTC, n=10), tg-control(TC, n=10) 및 tg-exercise(TE, n=10)으로 구분하고, 트레드밀 운동은 12주간 실행하였다(15m/min, 60min, 5 times/week). 운동 후 인지기능 능력을 확인하기 위해 수중미로검사를 실시하고, AD의 병리학적 특징인 아밀로이드 단백질, 신경세포사멸 및 미토콘드리아 항상성 기전(미토파지, 미토콘드리아 생합성)에 관련된 단백질들을 western blot과 immunohistochemistry를 통해 확인하였다. [결과] 그 결과, 트레드밀 운동은 올리고머 아밀로이드를 유의하게 감소시켰고, 세포사멸과 관련된 단백질(PUMA, Bax, Bcl-2)에도 긍정적인 효과를 나타냈다. 또한, 트레드밀 운동을 통해 PINK-1은 감소하고, parkin을 증가시켜 미토파지의 활성 억제가 일부 완화된 것으로 나타났다. 오토파지 핵심 마커인 LC3와 p62는 TC 집단에 비해 TE 집단에서 p62 발현을 유의하게 감소시키고, LC3-II/LC3-I ratio은 유의하지는 않지만 감소하는 경향이 나타나 미토파지의 활성을 증가시킨 것으로 확인되었다. 미토콘드리아 생합성과 관련된 단백질(SIRT-1, PGC-1α, Tfam 및 COX-IV)을 확인한 결과 트레드밀 운동을 통해 모든 단백질들의 발현이 일부 증가되는 것을 확인하였다. 마지막으로, 인지능력은 트레드밀 운동을 통해 수영 거리와 시간 모두 단축시켜 인지능력이 향상된 것으로 나타났다. [결론] 따라서 트레드밀 운동은 AD의 병리학적 특징인 아밀로이드 단백질의 수준을 감소시키고 미토파지의 활성과 미토콘드리아 기능향상을 유도하여 결과적으로 인지기능의 개선을 유도할 수 있는 효과적인 방법이라고 생각된다.

Abstract

[Purpose] The aim of this study was to investigate the effects of treadmill exercise on mitochondrial quality control in the APP/sw transgenic mice model of Alzheimer's disease(AD). [Methods] The experimental mice were divided into non-tg-control (NTC, n=10), tg-control (TC, n=10), and tg-exercise (TE, n=10), and treadmill exercise was conducted for 12 weeks (15m/min, 60min, 5 times/week). And then, we measured the cognitive function using MWM and the brain cortex was evaluated to determine whether any changes in the oligomer Aβ, apoptotic-related factors, mitophagy and mitochondrial biogenesis. [Results] As a result, treadmill exercise significantly reduced oligomer amyloid and also had a positive effect on proteins (PUMA, Bax, Bcl-2) associated with apoptosis. In addition, through the treadmill exercise, PINK-1 decreased, and increased parkin, showing that active inhibition of mitophagy has been partially relaxed. It has been confirmed that the key autophagy markers LC3 and p62 significantly reduce p62 expression in TE group compared to TC group, and that LC3-II/LC3-I ratio tended to decrease, although not significant, increasing the activity of mitophagy. Next, proteins related to mitochondrial biosynthesis (SIRT-1, PGC-1α, Tfam, and COX-IV) have been identified, and the treadmill exercise has confirmed that the expression of all proteins has increased in part. Finally, cognitive has been shown to improve cognitive by shortening both swimming distance and time through treadmill exercise. [Conclusions] Thus, our finding suggested treadmill exercise alleviates cognitive dysfunction by improving mitochondrial quality control(mitophagy, mitochondrial biogenesis) and neuronal cell death via reducing amyloid accumulation, which may play a role in a preventive strategy for AD.

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트레드밀 지구성 운동이 알츠하이머 형질전환 생쥐 뇌의 mitochondrial dynamic과 신경세포생존에 미치는 영향구정훈, 조인호한국운동생리학회 · 운동과학2016 · 제25권 제1호트레드밀 운동이 파킨슨 유도 모델 쥐의 α-synuclein 발현과 미토콘드리아 구조적 역동성에 미치는 영향구정훈한국운동생리학회 · 운동과학2016 · 제25권 제4호운동이 초기 알츠하이머형 마우스의 산화성 스트레스와 열쇼크단백질에 미치는 영향강민정, 조진경한국운동생리학회 · 운동과학2019 · 제28권 제4호트레드밀 운동이 streptozotocin 뇌실 처치로 유발된 알츠하이머 동물 모델 쥐의 신경염증과 신경세포사멸에 미치는 영향강은범국민체육진흥공단 한국스포츠과학원 · 체육과학연구2015 · 제26권 제1호지구성 운동과 MitoQ 섭취가 Alcl3로 유도된 알츠하이머 질환 동물 모델의 Tau 과인산화, 산화스트레스, 항산화 조절 요인, 미토콘드리아 기능 및 인지기능에 미치는 영향이정국, 정진희, 조준용, 최동훈한국운동생리학회 · 운동과학2021 · 제30권 제3호중강도 운동이 고지방식을 유도한 알츠하이머 치매 마우스의 시냅스 소포체 및 항산화 효소 발현에 미치는 영향김동현, 김인재한국운동생리학회 · 운동과학2020 · 제29권 제2호

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