지구성 운동과 MitoQ 섭취가 Alcl3로 유도된 알츠하이머 질환 동물 모델의 Tau 과인산화, 산화스트레스, 항산화 조절 요인, 미토콘드리아 기능 및 인지기능에 미치는 영향
Effect of Endurance Exercise and MitoQ Intake on Tau Hyperphosphorylation, Oxidative Stress, Antioxidant Modulating Factors, Mitochondrial Function, and Cognitive Function in Alcl3-Induced Alzheimer’s Disease Animal Model
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PURPOSE: This study aimed to investigate the effect of 8 weeks of endurance exercise and MitoQ intake on tau hyperphosphorylation, oxidative stress, antioxidant modulating factors, mitochondrial function, and cognitive function in an AlCl3-induced Alzheimer’s disease animal model. METHODS: For the experimental animals, 40 mg/kg of aluminum chloride (AlCl3) was diluted with physiological saline for 60 days and intraperitoneally injected to create an Alzheimer’s disease animal model. In addition, endurance exercise was performed at a speed of 12 m/min using a treadmill for laboratory animals for 8 weeks, and MitoQ was applied with a 100 μm concentration of negative water. The rats were randomly divided into five groups: a saline control group (NC, n=6), an AlCl3 injection group (AC, n=6), an AlCl3 injection and treadmill exercise group (AE, n=6), an AlCl3 injection and MitoQ group (AM, n=6), and an AlCl3 injection and treadmill exercise and MitoQ intake group (AEM, n=6). The SPSS program was used for statistical analyses. Differences between the groups in each variable were analyzed using the one-way ANOVA. RESULTS: Endurance exercise and MitoQ intake for 8 weeks showed positive results in cognitive function and decreased tau hyperphosphorylation in the animal model with Alzheimer’s disease. In addition, they reduced oxidative stress (4-HNE, MDA) and had a positive effect on antioxidant indicators (catalase, SOD-1, SOD-2). Finally, they exhibited a positive effect on factors related to mitochondrial function (PGC-1, Tfam). CONCLUSIONS: Eight weeks of endurance exercise and MitoQ intake are thought to have a positive effect in alleviating Alzheimer’s disease in terms of improving cognitive function through AlCl3 accumulation, tau hyperphosphorylation, oxidative stress, antioxidant modulating factors, and mitochondrial function.
Abstract
PURPOSE: This study aimed to investigate the effect of 8 weeks of endurance exercise and MitoQ intake on tau hyperphosphorylation, oxidative stress, antioxidant modulating factors, mitochondrial function, and cognitive function in an AlCl3-induced Alzheimer’s disease animal model. METHODS: For the experimental animals, 40 mg/kg of aluminum chloride (AlCl3) was diluted with physiological saline for 60 days and intraperitoneally injected to create an Alzheimer’s disease animal model. In addition, endurance exercise was performed at a speed of 12 m/min using a treadmill for laboratory animals for 8 weeks, and MitoQ was applied with a 100 μm concentration of negative water. The rats were randomly divided into five groups: a saline control group (NC, n=6), an AlCl3 injection group (AC, n=6), an AlCl3 injection and treadmill exercise group (AE, n=6), an AlCl3 injection and MitoQ group (AM, n=6), and an AlCl3 injection and treadmill exercise and MitoQ intake group (AEM, n=6). The SPSS program was used for statistical analyses. Differences between the groups in each variable were analyzed using the one-way ANOVA. RESULTS: Endurance exercise and MitoQ intake for 8 weeks showed positive results in cognitive function and decreased tau hyperphosphorylation in the animal model with Alzheimer’s disease. In addition, they reduced oxidative stress (4-HNE, MDA) and had a positive effect on antioxidant indicators (catalase, SOD-1, SOD-2). Finally, they exhibited a positive effect on factors related to mitochondrial function (PGC-1, Tfam). CONCLUSIONS: Eight weeks of endurance exercise and MitoQ intake are thought to have a positive effect in alleviating Alzheimer’s disease in terms of improving cognitive function through AlCl3 accumulation, tau hyperphosphorylation, oxidative stress, antioxidant modulating factors, and mitochondrial function.
참고문헌 (46)
- "Ministry of health and welfare", ~ (2019)
- Kawahara M, "Aluminum promotes the aggregation of alzheimer’s amyloid beta-protein in vitro", Biochem Biophys Res Commun, 198(2), pp.531~535 (1994)
- Tomljenovic L, "Aluminum and alzheimer's disease : after a century of controversy, is there a plausiblelink?", J Alzheimers Dis, 23, pp.567~598 (2011)
- Justin Thenmozhi A, "Neroprotective effect of hesperidin on aluminum chloride induced alzheimer’s disease in Wistar rats", Neurochem Res, 40(4), pp.767~776 (2015)
- Zaky A, "Apurinic", apyrimidinic endonuclease is a key modulator of aluminuminduced neuroinflammation, 2013, pp.14, 26~
- Walton JR, "Cognitive deterioration and associated pathology induced by chronic low-level aluminum ingestion in al translational rat model provides an explanation of alzheimer’s disease, tests for susceptibility and avenues for treatment", Int J Alzheimers Dis, pp.914947~ (2012)
- Yang X, "Bone impairment caused by AlCl3 is associated with activation of the JNK apoptotic pathway mediated by oxidative stress", Food Chem. Toxicol, 116, pp.307~314 (2018)
- Abulfadl YS, "Protective effects of thymoquinone on d-galactose and aluminum chloride induced neurotoxicity in rats : biochemical, histological and behavioral changes", Neurol Res, 40, pp.324~333 (2018)
- Harrington CR, "The molecular pathology of alzheimer's disease", Neuroimaging Clin N Am, 22, pp.11~22 (2012)
- Iqbal K, "Identification and localization of a Tau peptide to paired helical filaments of alzheimer disease", Proc Natl Acad Sci U S A, 86(14), pp.5646~5650 (1989)
- Lee VM, "A major submit of paired helical filaments and derivatized forms of normal Tau", Science, 251(4994), pp.675~678 (1991)
- 최주리, "흰쥐 대뇌세포의 저산소증 모델에서 황련의 활성산소 생성 억제와 신경세포사 억제", 생명과학회지, 18(3), pp.311~317 (2008), 한국생명과학회
- Mondragón-Rodríguez S, "Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for alzheimer’s disease", Oxid Med Cell Longev, pp.940603~ (2013)
- Jara C, "Genetic ablation of tau improves mitochondrial function and cognitive abilities in the hippocampus", Redox Biol, 18, pp.279~294 (2018)
- Morris GP, "Inconsistencies and controversies surrounding the amyloid hypothesis of alzheimer’s disease", Acta Neuropathol Commun, 2, pp.135~ (2014)
- Maliszewska-Cyna E, "The Benefits of Exercise and Metabolic Interventions for the Prevention and Early Treatment of alzheimer's Disease", Curr Alzheimer Res, 14(1), pp.47~60 (2017)
- Koo JH, "Treadmill exercise decreases amyloid-beta burdenpossibly via activation of SIRT-1 signaling in a mouse model of Alzheimer'sdisease", Exp Neurol, 288, pp.142~152 (2017)
- Moore G, "ACSM'sexercise management for persons with chronic diseases and disabilities" (2016), Human Kinetics
- Cai H, "Effect of exercise on cognitive function in chronic diseasepatients : a meta-analysis and systematic review of randomized controlledtrials", Clin Interv Aging, 12, pp.773~783 (2017)
- Albarracin SL, "Effects of natural antioxidants in neurodegenerative disease", Nutr Neurosci, 15, pp.1~9 (2012)
- Jin Y, "Molecular and functional interaction of the myokine irisin with physical exercise and alzheimer’s disease", Molecules, 23(12), pp.3229~ (2018)
- Saba K, "Energetics of excitatory and inhibitory neurotransmission in aluminum chloride model of alzheimer’s disease: reversal of behavioral and metabolic deficits by rasa sindoor", Front. Mol. Neurosci, 10, pp.323~ (2017)
- Shati AA, "Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup", Neuroscience, 175, pp.66~74 (2011)
- Okamoto M, "Hormetic effects by exercise on hippocampal neurogenesiswith glucocorticoid signaling", BrainPlast, 1, pp.149~158 (2015)
- Rodriguez-Cuenca S, "Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice", Free Radic Biol Med, 48, pp.161~172 (2010)
- Orta-Salazar E, "Análisis morfológico de la región del hipocampo asociado a una tarea conductual innata en el modelo de ratón transgénico(3xTg-AD)para la enfermedad de Alzheimer", Neurología, 28, pp.497~502 (2013)
- Deacon RM, "Burrowing in rodents : a sensitive method for detecting behavioral dysfunction", Nat Protoc, 1(1), pp.118~121 (2006)
- Ahmad Rather M, "Neuroprotective role of asiatic acid in aluminium chloride induced rat model of alzheimer's disease", Front Biosci(Schol Ed), 10, pp.262~275 (2018)
- Singh NA, "EGCG nanoparticles attenuate aluminum chloride Induced neurobehavioral deficits, beta amyloid and tau pathology in a rat model of alzheimer’s disease", Front Aging Neurosci, 10, pp.244~ (2018)
- John JA, "Selective brain-targeted antagonism of p38 MAPKα reduces hippocampal IL-1β levels and improves morris water maze performance in aged rats", J Alzheimers Dis, 48(1), pp.219227~ (2015)
- Yuan D, "Nest-building activity as a reproducible and long-term stroke deficit test in a mouse model of stroke", Brain Behav, 8(6), pp.e00993~ (2018)
- Deacon RM, "Age-dependent and-independent behavioral deficits in Tg2576mice", Behav Brain Res, 189(1), pp.126~138 (2008)
- Walker JM, "Beneficial effects of dietary EGCG and voluntary exercise on behavior in an alzheimer's disease mouse model", J Alzheimers Dis, 44(2), pp.561~572 (2013)
- Castorina A, "Early effects of aluminumchloride on beta-secretase mRNA expression in a neuronal model of beta-amyloidtoxicity", Cell Biol Toxicol, 26, pp.367~377 (2010)
- Maliszewska-Cyna E, "The benefits of exercise and metabolicInterventions for the prevention and early treatment of alzheimer's disease", Curr Alzheimer Res, 14, pp.47~60 (2017)
- Nigam SM, "Exercise and BDNF reduce abetaproduction by enhancing alpha-secretase processing of APP", J Neurochem, 142, pp.286~296 (2017)
- Choi SH, "Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model", Science, 361 (2018)
- Mc-manus MJ, "The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease", J Neurosci, 31(44), pp.15703~15715 (2011)
- Ma T, "Amyloid beta-induced impairments in hippocampal synaptic plasticity arerescued by decreasing mitochondrial superoxide", J Neurosci, 31, pp.5589~5595 (2011)
- Thapa A, "Dietary modulation of oxidative stress in alzheimer's disease", Int J Mol Sci, 18 (2017)
- 권기천, "지구성 운동이 알츠하이머 질환모델 동물의 저하된 뇌 인슐린 반응에 미치는 영향", 한국체육과학회지, 27(1), pp.689~699 (2018), 한국체육과학회[DOI]
- Peter Y, "Elevated Cu", Zn-SOD exacerbates radiation sensitivity and hematopoietic abnormalities of Atm-deficient mice, 2001, pp.20(7), 1538~1546
- Qin W, "PGC-1alpha expression decreases in the alzheimer disease brain as a function of dementia", Arch Neurol, 66(3), pp.352~361 (2009)
- Wang L, "Expression and localization of mitochondrial ferritin mRNA in alzheimer’s disease cerebral cortex", PLoS ONE, 9(7), pp.e22325~ (2011)
- Thomas RR, "Impaired complex-I mitochondrial biogenesis in parkinson disease frontal cortex", J Parkinsons Dis, 2(1), pp.67~76 (2012)
- 박노환, "트레드밀 지구성 운동이 streptozotocin으로 유발된 당뇨 흰쥐의 뇌에서 PGC-1α, GLUT-1, Tfam 단백질 및 항산화 효소(Cu, Zn-SOD, Mn-SOD)의 발현량에 미치는 영향", 생명과학회지, 21(3), pp.435~443 (2011), 한국생명과학회
