운동이 초기 알츠하이머형 마우스의 산화성 스트레스와 열쇼크단백질에 미치는 영향
Effects of Treadmill Running on Oxidative Stress and Heat Shock Protein in early stage of 3xTg-AD mice
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
PURPOSE: The mechanisms underlying the protective effects of exercise training against cognitive decline are not fully understood. This study aimed to investigate the effects of treadmill running on oxidative stress and heat shock protein levels in a mouse model of early stage triple transgenic Alzheimer’s disease (3xTg-AD). METHODS: We divided 5-month old 3xTg-AD mice (N=20) into the control (AD+CON, n=10) and exercise training (AD+EX, n=10) groups. Background strain mice were included as wild-type controls (WT, n=10). AD+EX mice were subjected to treadmill running at a speed of 15 m/min, 50 min/day, 5 days/week for 12 weeks. RESULTS: Treadmill running protected 3xTg-AD mice from cognitive decline and significantly suppressed the increase in soluble Aβ1-42 protein levels (AD+CON vs AD+EX, p=0.015) and the progression of oxidative damage. This was evidenced by significant increase in anti-oxidative protein levels such as superoxide dismutase-1 (SOD-1), heme oxygenase (HO-1) and heat shock protein 70 (HSP70) in the hippocampus of AD+EX mice compared to AD+CON mice. Moreover, the brain-derived neurotrophic factor (BDNF) and synaptic proteins such as PSD95 and synaptophysin were upregulated in AD+EX mice compared to AD+CON mice. CONCLUSIONS: Our findings support and extend previous studies reporting the preventive effects of exercise training on the pathological processes of the Alzheimer’s disease in the 3xTg AD mouse model.
Abstract
PURPOSE: The mechanisms underlying the protective effects of exercise training against cognitive decline are not fully understood. This study aimed to investigate the effects of treadmill running on oxidative stress and heat shock protein levels in a mouse model of early stage triple transgenic Alzheimer’s disease (3xTg-AD). METHODS: We divided 5-month old 3xTg-AD mice (N=20) into the control (AD+CON, n=10) and exercise training (AD+EX, n=10) groups. Background strain mice were included as wild-type controls (WT, n=10). AD+EX mice were subjected to treadmill running at a speed of 15 m/min, 50 min/day, 5 days/week for 12 weeks. RESULTS: Treadmill running protected 3xTg-AD mice from cognitive decline and significantly suppressed the increase in soluble Aβ1-42 protein levels (AD+CON vs AD+EX, p=0.015) and the progression of oxidative damage. This was evidenced by significant increase in anti-oxidative protein levels such as superoxide dismutase-1 (SOD-1), heme oxygenase (HO-1) and heat shock protein 70 (HSP70) in the hippocampus of AD+EX mice compared to AD+CON mice. Moreover, the brain-derived neurotrophic factor (BDNF) and synaptic proteins such as PSD95 and synaptophysin were upregulated in AD+EX mice compared to AD+CON mice. CONCLUSIONS: Our findings support and extend previous studies reporting the preventive effects of exercise training on the pathological processes of the Alzheimer’s disease in the 3xTg AD mouse model.
참고문헌 (24)
- Scheltens P, "Alzheimer’s disease", Lancet, 388(10043), pp.505~517 (2016)
- DeKosky ST, "Synapse loss in frontal cortex biopsies in Alzheimer’s disease : correlation with cognitive severity", Ann Neurol, 27(5), pp.457~464 (1990)
- Davies CA, "A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease", J Neurol Sci, 78(2), pp.151~164 (1987)
- You Joung Kim, "Prevalence and Trends of Dementia in Korea: A Systematic Review and Meta-Analysis", Journal of Korean Medical Science, 29(7), pp.903~912 (2014), 대한의학회
- Lim YY, "Association of beta-Amyloid and Apolipoprotein E epsilon4With Memory Decline in Preclinical Alzheimer Disease", JAMA Neurol, 75(4), pp.488~494 (2018)
- Chong FP, "Tau Proteins and Tauopathies in Alzheimer’s Disease", Cell Mol Neurobiol, 38(5), pp.965~980 (2018)
- Maiti P, "Molecular chaperone dysfunction in neurodegenerative diseases and effects of curcumin", Biomed Res Int, 2014, pp.495091~ (2014)
- Kakkar V, "Barcoding heat shock proteins to human diseases : looking beyond the heat shock response", Dis Model Mech, 7(4), pp.421~434 (2014)
- Ellis RJ, "Molecular chaperones : assisting assembly in addition to folding", Trends Biochem Sci, 31(7), pp.395~401 (2006)
- Schmitt E, "Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant", Cancer Res, 63(23), pp.8233~8240 (2003)
- Hoshino T, "Suppression of Alzheimer’s disease-related phenotypes by expression of heat shock protein 70 in mice", J Neurosci, 31(14), pp.5225~5234 (2011)
- Tonnies E, "Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease", J Alzheimers Dis, 57(4), pp.1105~1121 (2017)
- Kamat PK, "Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer’s Disease : Understanding the Therapeutics Strategies", Mol Neurobiol, 53(1), pp.648~661 (2016)
- Apelt J, "Aging-related increase in oxidative stress correlates with developmental pattern of beta-secretase activity and beta-amyloid plaque formation in transgenic Tg2576mice with Alzheimer-like pathology", Int J Dev Neurosci, 22(7), pp.475~484 (2004)
- Mota SI, "Oxidative stress involving changes in Nrf2 and ER stress in early stages of Alzheimer’s disease", Biochim Biophys Acta, 1852(7), pp.1428~1441 (2015)
- Cho J, "Treadmill Running Reverses Cognitive Declines due to Alzheimer Disease", Med Sci Sports Exerc, 47(9), pp.1814~1824 (2015)
- Wu C, "Beneficial Effects of Exercise Pretreatment in a Sporadic Alzheimer’s Rat Model", Med Sci Sports Exerc, 50(5), pp.945~956 (2018)
- Belviranli M, "Voluntary, involuntary and forced exercises almost equally reverse behavioral impairment by regulating hippocampal neurotrophic factors and oxidative stress in experimental Alzheimer’s disease model", Behav Brain Res, 364, pp.245~255 (2019)
- Lu Y, "Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease", J Alzheimers Dis, 56(4), pp.1469~1484 (2017)
- Oddo S, "Triple-transgenic model of Alzheimer’s disease with plaques and tangles : intracellular Abeta and synaptic dysfunction", Neuron, 39(3), pp.409~421 (2003)
- Leger M, "Object recognition test in mice", Nat Protoc, 8(12), pp.2531~2537 (2013)
- Liu HL, "Long-term treadmill exercise inhibits the progression of Alzheimer’s disease-like neuropathology in the hippocampus of APP", PS1 transgenic mice, 2013, pp.256, 261~272
- Zhao G, "Treadmill exercise enhances synaptic plasticity, but does not alter beta-amyloid deposition in hippocampi of aged APP", PS1 transgenic mice, 2015, pp.298, 357~366
- Moore KM, "A spectrum of exercise training reduces soluble Abeta in a dose-dependent manner in a mouse model of Alzheimer’s disease", Neurobiol Dis, 85, pp.218~224 (2016)