The effect of continuous aerobic exercise on hippocampal clusterin level, memory efficiency and exercise performance in aged rat model of Alzheimer's disease

Document Type : Research Paper

Authors

1 Department of Sports Sciences, Faculty of Educational Sciences and Psychology, Shahid Madani University of Azerbaijan, Tabriz, Iran.

2 Department of Sports Sciences, Faculty of Educational Sciences and Psychology, Shahid Madani University of Azerbaijan, Tabriz, Iran

3 Department of Biology, Faculty of Basic Sciences, Azerbaijan Shahid Madani University, Tabriz, Iran.

10.22080/jaep.2023.25325.2138

Abstract

Objectives: Alzheimer's (AD) is a chronic disease that destroys nerve cells, which eventually destroys the ability to do the simplest tasks. Alzheimer is caused by the accumulation of amyloid-beta (Aβ) peptides in the brain. Clusterin (CLU) interacts with Aβ and regulates its clearance from the brain. Studying the types of exercise activities and finding the best type is considered as a way to control Alzheimer's. The purpose of this research was to study the effect of six weeks of continuous aerobic training on CLU value, memory efficiency and exercise performance.
Methods: 40 aged (11-month-old) male Wistar rats randomly divided into four groups of 10, including the patient training, 2: patient control, 3: healthy training, and 4: healthy control groups. The rats performed the relevant exercises training for six weeks by repeating five sessions per week. CLU was measured by ELISA method, memory and exercise performance were measured by new object recognition test and maximum exercise capacity test respectively. One-way analysis of variance and Tukey's post hoc test, were used for statistical analysis.
Results: The amount of CLU in the hippocampus in the patient training group was significantly reduced compared to the patient control group (P<0.05). Also, improvement of memory performance was observed in the patient training group compared to the patient control group (P<0.05) and exercise performance increased in the patient training and healthy training groups compared to the control group (P<0.05).
Conclusion: According to the results of this research, continuous aerobic training during six weeks improves memory efficiency and exercise performance, as well as reducing clusterin in the hippocampus.

Highlights

## Sengoku R. Aging and Alzheimer's disease pathology. Neuropathology. 2020; 40(1):22-9.##Gronek P, Balko S, Gronek J, Zajac A, Maszczyk A, Celka R, et al. Physical activity and Alzheimer’s disease: a narrative review. Aging and disease. 2019; 10(6):1282.##Zavvari F, Karimzadeh F. A review on the behavioral tests for learning and memory assessments in rat. The Neuroscience Journal of Shefaye Khatam. 2017; 5(4):110-24.##Graham N, Warner J. Alzheimer's Disease and Other Dementias: Family Doctor Publications Limited; 2009.##Wang Y-J, Zhou H-D, Zhou X-F. Clearance of amyloid-beta in Alzheimer's disease: progress, problems and perspectives. Drug discovery today. 2006; 11(19-20):931-8.##Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell. 2015; 163(5):1064-78.##Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K, et al. Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance. Nature neuroscience. 2015; 18(7):978-87.##Moezzi S-M-I, Mozafari N, Fazel-Hoseini S-M, Nadimi-Parashkoohi S, Abbasi H, Ashrafi H, et al. Apolipoprotein J in Alzheimer’s disease: Shedding light on its role with cell signaling pathway perspective and possible therapeutic approaches. ACS Chemical Neuroscience. 2020; 11(24):4060-72.## Rizzi F, Bettuzzi S. The clusterin paradigm in prostate and breast carcinogenesis. Endocrine-related cancer. 2010; 17(1):R1.##Mulder SD, Nielsen HM, Blankenstein MA, Eikelenboom P, Veerhuis R. Apolipoproteins E and J interfere with amyloid‐beta uptake by primary human astrocytes and microglia in vitro. Glia. 2014; 62(4):493-503.##Suss O, Reichmann D. Protein plasticity underlines activation and function of ATP-independent chaperones. Frontiers in Molecular Biosciences. 2015; 2:43.##Li X, Ma Y, Wei X, Li Y, Wu H, Zhuang J, et al. Clusterin in Alzheimer’s disease: a player in the biological behavior of amyloid-beta. Neuroscience bulletin. 2014; 30(1):162-8.##Bargi R, Salmani H, Asgharzadeh Yazdi F, Hosseini M. Inflammation and the brain disorders: a review. The Neuroscience Journal of Shefaye Khatam. 2017; 5(3):68-82.##De Miguel Z, Betley MJ, Willoughby D, Lehallier B, Olsson N, Bonanno L, et al. Exercise conditioned plasma dampens inflammation via clusterin and boosts memory. bioRxiv. 2019:775288##Valenzuela PL, Castillo-Garcia A, Morales JS, de la Villa P, Hampel H, Emanuele E, et al. Exercise benefits on Alzheimer’s disease: State-of-the-science. Ageing research reviews. 2020; 62:101108.##Steinberg M, Leoutsakos JMS, Podewils LJ, Lyketsos C. Evaluation of a home‐based exercise program in the treatment of Alzheimer's disease: The Maximizing Independence in Dementia (MIND) study. International Journal of Geriatric Psychiatry: A journal of the psychiatry of late life and allied sciences. 2009; 24(7):680-5.##Liu H-l, Zhao G, Zhang H. Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice. Behavioural brain research. 2013; 256:261-72.##Pinto A, van Praag H. An exercise infusion benefits brain function. Cell Research. 2022; 32(3):223-4.##Darweesh SK, De Vries NM, Helmich RC, Verbeek MM, Schwarzschild MA, Bloem BR. Inhibition of Neuroinflammation May Mediate the Disease-Modifying Effects of Exercise: Implications for Parkinson’s Disease. Journal of Parkinson's disease. 2022(Preprint):1-4.## De Miguel Z, Khoury N, Betley MJ, Lehallier B, Willoughby D, Olsson N, et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature. 2021; 600(7889):494-9.##Pattanashetti LA, Taranalli AD, Parvatrao V, Malabade RH, Kumar D. Evaluation of neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats. Indian Journal of Pharmacology. 2017; 49(1):60.## Williams CJ, Gurd BJ, Bonafiglia JT, Voisin S, Li Z, Harvey N, et al. A multi-center comparison of O2peak trainAβility between interval training and moderate intensity continuous training. Frontiers in physiology. 2019; 10:19.## Feter N, Spanevello RM, Soares MSP, Spohr L, Pedra NS, Bona NP, et al. How does physical activity and different models of exercise training affect oxidative parameters and memory? Physiology & behavior. 2019; 201:42-52.##Qin F, Dong Y, Wang S, Xu M, Wang Z, Qu C, et al. Maximum oxygen consumption and quantification of exercise intensity in untrained male Wistar rats. Scientific Reports. 2020; 10(1):1-8.##Nuutinen T, Suuronen T, Kauppinen A, Salminen A. Clusterin: a forgotten player in Alzheimer's disease. Brain research reviews. 2009; 61(2):89-104.##Versele R, Corsi M, Fuso A, Sevin E, Businaro R, Gosselet F, et al. Ketone bodies promote amyloid-β1–40 clearance in a human in vitro blood–brain barrier model.##Desikan RS, Thompson WK, Holland D, Hess CP, Brewer JB, Zetterberg H, et al. THe role of clusterin in amyloid-β–associated neurodegeneration. JAMA neurology. 2014; 71(2):180-7.## Schuermann B, Wiese B, Bickel H, Weyerer S, Riedel-Heller SG, Pentzek M, et al. Association of the Alzheimer's disease clusterin risk allele with plasma clusterin concentration. Journal of Alzheimer's Disease. 2011; 25(3):421-4.##Stranahan A, Martin B, Maudsley S. Anti-inflammatory effects of physical activity in relationship to improved cognitive status in humans and mouse models of Alzheimer's disease. Current Alzheimer Research. 2012; 9(1):86-92.##Sun L-n, Qi J-s, Gao R. Physical exercise reserved amyloid-beta induced brain dysfunctions by regulating hippocampal neurogenesis and inflammatory response via MAPK signaling. Brain Research. 2018; 1697:1-9.##Morris JK, Vidoni ED, Johnson DK, Van Sciver A, Mahnken JD, Honea RA, et al. Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial. PloS one. 2017; 12(2):e0170547.##Yuede CM, Zimmerman SD, Dong H, Kling MJ, Bero AW, Holtzman DM, et al. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg 2576 mouse model of Alzheimer's disease. Neurobiology of disease. 2009; 35(3):426-32##

Keywords

References

## Sengoku R. Aging and Alzheimer's disease pathology. Neuropathology. 2020; 40(1):22-9.##Gronek P, Balko S, Gronek J, Zajac A, Maszczyk A, Celka R, et al. Physical activity and Alzheimer’s disease: a narrative review. Aging and disease. 2019; 10(6):1282.##Zavvari F, Karimzadeh F. A review on the behavioral tests for learning and memory assessments in rat. The Neuroscience Journal of Shefaye Khatam. 2017; 5(4):110-24.##Graham N, Warner J. Alzheimer's Disease and Other Dementias: Family Doctor Publications Limited; 2009.##Wang Y-J, Zhou H-D, Zhou X-F. Clearance of amyloid-beta in Alzheimer's disease: progress, problems and perspectives. Drug discovery today. 2006; 11(19-20):931-8.##Zhao Z, Nelson AR, Betsholtz C, Zlokovic BV. Establishment and dysfunction of the blood-brain barrier. Cell. 2015; 163(5):1064-78.##Zhao Z, Sagare AP, Ma Q, Halliday MR, Kong P, Kisler K, et al. Central role for PICALM in amyloid-β blood-brain barrier transcytosis and clearance. Nature neuroscience. 2015; 18(7):978-87.##Moezzi S-M-I, Mozafari N, Fazel-Hoseini S-M, Nadimi-Parashkoohi S, Abbasi H, Ashrafi H, et al. Apolipoprotein J in Alzheimer’s disease: Shedding light on its role with cell signaling pathway perspective and possible therapeutic approaches. ACS Chemical Neuroscience. 2020; 11(24):4060-72.## Rizzi F, Bettuzzi S. The clusterin paradigm in prostate and breast carcinogenesis. Endocrine-related cancer. 2010; 17(1):R1.##Mulder SD, Nielsen HM, Blankenstein MA, Eikelenboom P, Veerhuis R. Apolipoproteins E and J interfere with amyloid‐beta uptake by primary human astrocytes and microglia in vitro. Glia. 2014; 62(4):493-503.##Suss O, Reichmann D. Protein plasticity underlines activation and function of ATP-independent chaperones. Frontiers in Molecular Biosciences. 2015; 2:43.##Li X, Ma Y, Wei X, Li Y, Wu H, Zhuang J, et al. Clusterin in Alzheimer’s disease: a player in the biological behavior of amyloid-beta. Neuroscience bulletin. 2014; 30(1):162-8.##Bargi R, Salmani H, Asgharzadeh Yazdi F, Hosseini M. Inflammation and the brain disorders: a review. The Neuroscience Journal of Shefaye Khatam. 2017; 5(3):68-82.##De Miguel Z, Betley MJ, Willoughby D, Lehallier B, Olsson N, Bonanno L, et al. Exercise conditioned plasma dampens inflammation via clusterin and boosts memory. bioRxiv. 2019:775288##Valenzuela PL, Castillo-Garcia A, Morales JS, de la Villa P, Hampel H, Emanuele E, et al. Exercise benefits on Alzheimer’s disease: State-of-the-science. Ageing research reviews. 2020; 62:101108.##Steinberg M, Leoutsakos JMS, Podewils LJ, Lyketsos C. Evaluation of a home‐based exercise program in the treatment of Alzheimer's disease: The Maximizing Independence in Dementia (MIND) study. International Journal of Geriatric Psychiatry: A journal of the psychiatry of late life and allied sciences. 2009; 24(7):680-5.##Liu H-l, Zhao G, Zhang H. Long-term treadmill exercise inhibits the progression of Alzheimer's disease-like neuropathology in the hippocampus of APP/PS1 transgenic mice. Behavioural brain research. 2013; 256:261-72.##Pinto A, van Praag H. An exercise infusion benefits brain function. Cell Research. 2022; 32(3):223-4.##Darweesh SK, De Vries NM, Helmich RC, Verbeek MM, Schwarzschild MA, Bloem BR. Inhibition of Neuroinflammation May Mediate the Disease-Modifying Effects of Exercise: Implications for Parkinson’s Disease. Journal of Parkinson's disease. 2022(Preprint):1-4.## De Miguel Z, Khoury N, Betley MJ, Lehallier B, Willoughby D, Olsson N, et al. Exercise plasma boosts memory and dampens brain inflammation via clusterin. Nature. 2021; 600(7889):494-9.##Pattanashetti LA, Taranalli AD, Parvatrao V, Malabade RH, Kumar D. Evaluation of neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats. Indian Journal of Pharmacology. 2017; 49(1):60.## Williams CJ, Gurd BJ, Bonafiglia JT, Voisin S, Li Z, Harvey N, et al. A multi-center comparison of O2peak trainAβility between interval training and moderate intensity continuous training. Frontiers in physiology. 2019; 10:19.## Feter N, Spanevello RM, Soares MSP, Spohr L, Pedra NS, Bona NP, et al. How does physical activity and different models of exercise training affect oxidative parameters and memory? Physiology & behavior. 2019; 201:42-52.##Qin F, Dong Y, Wang S, Xu M, Wang Z, Qu C, et al. Maximum oxygen consumption and quantification of exercise intensity in untrained male Wistar rats. Scientific Reports. 2020; 10(1):1-8.##Nuutinen T, Suuronen T, Kauppinen A, Salminen A. Clusterin: a forgotten player in Alzheimer's disease. Brain research reviews. 2009; 61(2):89-104.##Versele R, Corsi M, Fuso A, Sevin E, Businaro R, Gosselet F, et al. Ketone bodies promote amyloid-β1–40 clearance in a human in vitro blood–brain barrier model.##Desikan RS, Thompson WK, Holland D, Hess CP, Brewer JB, Zetterberg H, et al. THe role of clusterin in amyloid-β–associated neurodegeneration. JAMA neurology. 2014; 71(2):180-7.## Schuermann B, Wiese B, Bickel H, Weyerer S, Riedel-Heller SG, Pentzek M, et al. Association of the Alzheimer's disease clusterin risk allele with plasma clusterin concentration. Journal of Alzheimer's Disease. 2011; 25(3):421-4.##Stranahan A, Martin B, Maudsley S. Anti-inflammatory effects of physical activity in relationship to improved cognitive status in humans and mouse models of Alzheimer's disease. Current Alzheimer Research. 2012; 9(1):86-92.##Sun L-n, Qi J-s, Gao R. Physical exercise reserved amyloid-beta induced brain dysfunctions by regulating hippocampal neurogenesis and inflammatory response via MAPK signaling. Brain Research. 2018; 1697:1-9.##Morris JK, Vidoni ED, Johnson DK, Van Sciver A, Mahnken JD, Honea RA, et al. Aerobic exercise for Alzheimer's disease: A randomized controlled pilot trial. PloS one. 2017; 12(2):e0170547.##Yuede CM, Zimmerman SD, Dong H, Kling MJ, Bero AW, Holtzman DM, et al. Effects of voluntary and forced exercise on plaque deposition, hippocampal volume, and behavior in the Tg 2576 mouse model of Alzheimer's disease. Neurobiology of disease. 2009; 35(3):426-32##
Journal of Applied Exercise Physiology
Volume 18, Issue 35
April 2022
Pages 139-151

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History

  • Receive Date: 17 April 2023
  • Revise Date: 17 May 2023
  • Accept Date: 16 June 2023

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