Comparison of the Effects of High-Intensity Interval Training and Activity in Motor Enriched Environment on the Expression of Leptin and Brain-Derived Neurotrophic Factor Proteins in the Hippocampal Tissue of Rats with Alzheimer’s Disease

Mohammadishad, Marsa; Kordi, Mohammad Reza; Choobine, Siroos

doi:10.22059/jsb.2022.344465.1539

Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license

Authors

¹ Department of Exercise Physiology, Kish International Campus, University of Tehran, Kish, Iran.

² Corresponding Author, Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran.

³ Department of Exercise Physiology, Faculty of Sport Sciences and Health, University of Tehran, Tehran, Iran.

https://doi.org/10.22059/jsb.2022.344465.1539

Abstract

Introduction: The effect of physical activity on some cognitive mechanisms in Alzheimer's Disease (AD) patients is not yet well understood. Therefore, this study aimed to compare the effect of High-Intensity Interval Training (HIIT) and Motor Enriched Environment Activity (MEEA) on the expression of leptin and Brain-Derived Neurotrophic Factor (BDNF) in the hippocampal tissue of rats with AD.
Methods: In this experimental study, 24 rats with AD were divided into AD control, HIIT, and MEEA groups. The Sham (SH) group was considered to evaluate the effect of surgery and saline injection and the Healthy control (HC) group was considered to evaluate the effect of AD induction. The HIIT group trained for eight weeks, five sessions per week, and each session consisted of nine 90-second intervals at 85% of maximum speed intensity, and the MEEA group was placed in special motor-enriched cages. One-way analysis of variance and Tukey's post hoc tests were used to analyze the data (P≤0.05).
Results: The results showed that in the AD group, BDNF levels were lower (P=0.001), and leptin levels were higher (P=0.001) than in the HC group. In the HIIT group, leptin levels were lower (P=0.005), and BDNF levels were higher (P=0.019) than in the AD group. The two training groups showed no significant difference in leptin (P=0.72) and BDNF (P=0.65) levels.
Conclusion: Both HIIT and MEEA appear to be effective in improving neurotrophins and hippocampal metabolism, but the effect of HIIT is more favorable due to exercise-induced adaptation.

Keywords

Main Subjects

Exercise Physiology

References

1] Cummings J, Lee G, Zhong K, Fonseca J, Taghva K. Alzheimer's disease drug development pipeline: 2021. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2021;7(1):e12179. 10.1002/trc2.12179.

[2] Uddin MJ, Kim EH, Hannan MA, Ha H. Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling. Antioxidants (Basel). 2021;10(2). 10.3390/antiox10020258

[3] Fracassi A, Marcatti M, Zolochevska O, Tabor N, Woltjer R, Moreno S, et al. Oxidative Damage and Antioxidant Response in Frontal Cortex of Demented and Nondemented Individuals with Alzheimer's Neuropathology. J Neurosci. 2021;41(3):538-54. 10.1523/JNEUROSCI.0295-20.2020

[4] Li C, Meng F, Lei Y, Liu J, Liu J, Zhang J, et al. Leptin regulates exon-specific transcription of the Bdnf gene via epigenetic modifications mediated by an AKT/p300 HAT cascade. Molecular psychiatry. 2021;26(8):3701-22. 10.1038/s41380-020-00922-0

[5] Hamilton K, Harvey J. The neuronal actions of leptin and the implications for treating alzheimer’s disease. Pharmaceuticals. 2021;14(1):52. 10.3390/ph14010052

[6] Mueller K, Möller HE, Horstmann A, Busse F, Lepsien J, Blüher M, et al. Physical exercise in overweight to obese individuals induces metabolic-and neurotrophic-related structural brain plasticity. Frontiers in human neuroscience. 2015;9:372. 10.3389/fnhum.2015.00372

[7] Hosseini SA, Salehi O, Keikhosravi F, Hassanpour G, Ardakani HD, Farkhaie F, et al. Mental health benefits of exercise and genistein in elderly rats. Experimental aging research. 2022;48(1):42-57. 10.1080/0361073X.2021.1918473

[8] Jamali A, Shahrbanian S, Morteza Tayebi S. The effects of exercise training on the brain-derived neurotrophic factor (BDNF) in the patients with type 2 diabetes: A systematic review of the randomized controlled trials. Journal of Diabetes & Metabolic Disorders. 2020;19:633-43 10.1007/s40200-020-00529-w

[9] Glud M, Christiansen T, Larsen L, Richelsen B, Bruun J. Changes in circulating BDNF in relation to sex, diet, and exercise: a 12-week randomized controlled study in overweight and obese participants. Journal of obesity. 2019;2019. 10.1155/2019/4537274

[10] Bozorgi AD, Behboudi L, Hosseini SA, Rasoli MH. Effect of voluntary and forced training with royal jelly consumption on learning and spatial memory of rat model of alzheimer’s disease. Jundishapur Journal of Chronic Disease Care. 2020;9(1). 10.5812/jjcdc.97261.

[11] Dinoff A, Herrmann N, Swardfager W, Liu CS, Sherman C, Chan S, et al. The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PloS one. 2016;11(9):e0163037. 10.1371/journal.pone.0163037

[12] Kamat PK. Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism. Neural regeneration research. 2015;10(7):1050. 10.4103/1673-5374.160076

[13] Fayazmilani R, HaghParast A, Rostami S. Effect of Combined Training and Play in an Enriched Environment During Prepuberty Period on Hippocampal. Sport Physiology. Spring 2021; 13 (49): 199-222. Doi: 10.22089/spj.2020.9395.2065(In Persian).

[14] Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, et al. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behavioural brain research. 2006;171(1):9-16. 10.1016/j.bbr.2006.03.009.

[15] Sodhi RK, Singh N. All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013;40:38-46. 10.1016/j.pnpbp.2012.09.012

[16] Calió ML, Mosini AC, Marinho DS, Salles GN, Massinhani FH, Ko GM, et al. Leptin enhances adult neurogenesis and reduces pathological features in a transgenic mouse model of Alzheimer’s disease. Neurobiology of disease. 2021;148:105219. 10.1016/j.nbd.2020.105219

[17] Yook JS, Rakwal R, Shibato J, Takahashi K, Koizumi H, Shima T, et al. Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory. Proceedings of the National Academy of Sciences. 2019;116(22):10988-93. 10.1073/pnas.1815197116

[18] Salehi OR, Hoseini A. The effects of endurance trainings on serum BDNF and insulin levels in streptozotocin-induced diabetic rats. Shefaye Khatam. 2017;5(2):52-61. (In Persian).10.18869/acadpub.shefa.5.2.52

[19] Marin Bosch B, Bringard A, Logrieco MG, Lauer E, Imobersteg N, Thomas A, et al. A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men. Scientific reports. 2021;11(1):14371. 10.1038/s41598-021-93813-5

[20] Salehi OR, Hosseini SA, Farkhaie F, Farzanegi P, Zar A. The effect of moderate intensity endurance training with genistein on brain-derived neurotrophic factor and tumor necrosis factor-α in diabetic rats. Journal of nutrition, fasting and health. 2019;7(1):44-51. 10.22038/JNFH.2019.37231.1163

[21] Murawska-Ciałowicz E, de Assis GG, Clemente FM, Feito Y, Stastny P, Zuwała-Jagiełło J, et al. Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test. Scientific reports. 2021;11(1):8599. 10.1038/s41598-021-88069-y

Journal of Sport Biosciences

Comparison of the Effects of High-Intensity Interval Training and Activity in Motor Enriched Environment on the Expression of Leptin and Brain-Derived Neurotrophic Factor Proteins in the Hippocampal Tissue of Rats with Alzheimer’s Disease

References

References

1] Cummings J, Lee G, Zhong K, Fonseca J, Taghva K. Alzheimer's disease drug development pipeline: 2021. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2021;7(1):e12179. 10.1002/trc2.12179.

[2] Uddin MJ, Kim EH, Hannan MA, Ha H. Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling. Antioxidants (Basel). 2021;10(2). 10.3390/antiox10020258

[3] Fracassi A, Marcatti M, Zolochevska O, Tabor N, Woltjer R, Moreno S, et al. Oxidative Damage and Antioxidant Response in Frontal Cortex of Demented and Nondemented Individuals with Alzheimer's Neuropathology. J Neurosci. 2021;41(3):538-54. 10.1523/JNEUROSCI.0295-20.2020

[4] Li C, Meng F, Lei Y, Liu J, Liu J, Zhang J, et al. Leptin regulates exon-specific transcription of the Bdnf gene via epigenetic modifications mediated by an AKT/p300 HAT cascade. Molecular psychiatry. 2021;26(8):3701-22. 10.1038/s41380-020-00922-0

[5] Hamilton K, Harvey J. The neuronal actions of leptin and the implications for treating alzheimer’s disease. Pharmaceuticals. 2021;14(1):52. 10.3390/ph14010052

[6] Mueller K, Möller HE, Horstmann A, Busse F, Lepsien J, Blüher M, et al. Physical exercise in overweight to obese individuals induces metabolic-and neurotrophic-related structural brain plasticity. Frontiers in human neuroscience. 2015;9:372. 10.3389/fnhum.2015.00372

[7] Hosseini SA, Salehi O, Keikhosravi F, Hassanpour G, Ardakani HD, Farkhaie F, et al. Mental health benefits of exercise and genistein in elderly rats. Experimental aging research. 2022;48(1):42-57. 10.1080/0361073X.2021.1918473

[9] Glud M, Christiansen T, Larsen L, Richelsen B, Bruun J. Changes in circulating BDNF in relation to sex, diet, and exercise: a 12-week randomized controlled study in overweight and obese participants. Journal of obesity. 2019;2019. 10.1155/2019/4537274

[10] Bozorgi AD, Behboudi L, Hosseini SA, Rasoli MH. Effect of voluntary and forced training with royal jelly consumption on learning and spatial memory of rat model of alzheimer’s disease. Jundishapur Journal of Chronic Disease Care. 2020;9(1). 10.5812/jjcdc.97261.

[11] Dinoff A, Herrmann N, Swardfager W, Liu CS, Sherman C, Chan S, et al. The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PloS one. 2016;11(9):e0163037. 10.1371/journal.pone.0163037

[12] Kamat PK. Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism. Neural regeneration research. 2015;10(7):1050. 10.4103/1673-5374.160076

[13] Fayazmilani R, HaghParast A, Rostami S. Effect of Combined Training and Play in an Enriched Environment During Prepuberty Period on Hippocampal. Sport Physiology. Spring 2021; 13 (49): 199-222. Doi: 10.22089/spj.2020.9395.2065(In Persian).

[14] Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, et al. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behavioural brain research. 2006;171(1):9-16. 10.1016/j.bbr.2006.03.009.

[15] Sodhi RK, Singh N. All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013;40:38-46. 10.1016/j.pnpbp.2012.09.012

[16] Calió ML, Mosini AC, Marinho DS, Salles GN, Massinhani FH, Ko GM, et al. Leptin enhances adult neurogenesis and reduces pathological features in a transgenic mouse model of Alzheimer’s disease. Neurobiology of disease. 2021;148:105219. 10.1016/j.nbd.2020.105219

[17] Yook JS, Rakwal R, Shibato J, Takahashi K, Koizumi H, Shima T, et al. Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory. Proceedings of the National Academy of Sciences. 2019;116(22):10988-93. 10.1073/pnas.1815197116

[18] Salehi OR, Hoseini A. The effects of endurance trainings on serum BDNF and insulin levels in streptozotocin-induced diabetic rats. Shefaye Khatam. 2017;5(2):52-61. (In Persian).10.18869/acadpub.shefa.5.2.52

[19] Marin Bosch B, Bringard A, Logrieco MG, Lauer E, Imobersteg N, Thomas A, et al. A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men. Scientific reports. 2021;11(1):14371. 10.1038/s41598-021-93813-5

[20] Salehi OR, Hosseini SA, Farkhaie F, Farzanegi P, Zar A. The effect of moderate intensity endurance training with genistein on brain-derived neurotrophic factor and tumor necrosis factor-α in diabetic rats. Journal of nutrition, fasting and health. 2019;7(1):44-51. 10.22038/JNFH.2019.37231.1163

[21] Murawska-Ciałowicz E, de Assis GG, Clemente FM, Feito Y, Stastny P, Zuwała-Jagiełło J, et al. Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test. Scientific reports. 2021;11(1):8599. 10.1038/s41598-021-88069-y

Volume 15, Issue 2 - Serial Number 96
May 2023
Pages 5-14

Comparison of the Effects of High-Intensity Interval Training and Activity in Motor Enriched Environment on the Expression of Leptin and Brain-Derived Neurotrophic Factor Proteins in the Hippocampal Tissue of Rats with Alzheimer’s Disease

References

References

1] Cummings J, Lee G, Zhong K, Fonseca J, Taghva K. Alzheimer's disease drug development pipeline: 2021. Alzheimer's & Dementia: Translational Research & Clinical Interventions. 2021;7(1):e12179. 10.1002/trc2.12179.

[2] Uddin MJ, Kim EH, Hannan MA, Ha H. Pharmacotherapy against Oxidative Stress in Chronic Kidney Disease: Promising Small Molecule Natural Products Targeting Nrf2-HO-1 Signaling. Antioxidants (Basel). 2021;10(2). 10.3390/antiox10020258

[3] Fracassi A, Marcatti M, Zolochevska O, Tabor N, Woltjer R, Moreno S, et al. Oxidative Damage and Antioxidant Response in Frontal Cortex of Demented and Nondemented Individuals with Alzheimer's Neuropathology. J Neurosci. 2021;41(3):538-54. 10.1523/JNEUROSCI.0295-20.2020

[4] Li C, Meng F, Lei Y, Liu J, Liu J, Zhang J, et al. Leptin regulates exon-specific transcription of the Bdnf gene via epigenetic modifications mediated by an AKT/p300 HAT cascade. Molecular psychiatry. 2021;26(8):3701-22. 10.1038/s41380-020-00922-0

[5] Hamilton K, Harvey J. The neuronal actions of leptin and the implications for treating alzheimer’s disease. Pharmaceuticals. 2021;14(1):52. 10.3390/ph14010052

[6] Mueller K, Möller HE, Horstmann A, Busse F, Lepsien J, Blüher M, et al. Physical exercise in overweight to obese individuals induces metabolic-and neurotrophic-related structural brain plasticity. Frontiers in human neuroscience. 2015;9:372. 10.3389/fnhum.2015.00372

[7] Hosseini SA, Salehi O, Keikhosravi F, Hassanpour G, Ardakani HD, Farkhaie F, et al. Mental health benefits of exercise and genistein in elderly rats. Experimental aging research. 2022;48(1):42-57. 10.1080/0361073X.2021.1918473

[9] Glud M, Christiansen T, Larsen L, Richelsen B, Bruun J. Changes in circulating BDNF in relation to sex, diet, and exercise: a 12-week randomized controlled study in overweight and obese participants. Journal of obesity. 2019;2019. 10.1155/2019/4537274

[10] Bozorgi AD, Behboudi L, Hosseini SA, Rasoli MH. Effect of voluntary and forced training with royal jelly consumption on learning and spatial memory of rat model of alzheimer’s disease. Jundishapur Journal of Chronic Disease Care. 2020;9(1). 10.5812/jjcdc.97261.

[11] Dinoff A, Herrmann N, Swardfager W, Liu CS, Sherman C, Chan S, et al. The effect of exercise training on resting concentrations of peripheral brain-derived neurotrophic factor (BDNF): a meta-analysis. PloS one. 2016;11(9):e0163037. 10.1371/journal.pone.0163037

[12] Kamat PK. Streptozotocin induced Alzheimer's disease like changes and the underlying neural degeneration and regeneration mechanism. Neural regeneration research. 2015;10(7):1050. 10.4103/1673-5374.160076

[13] Fayazmilani R, HaghParast A, Rostami S. Effect of Combined Training and Play in an Enriched Environment During Prepuberty Period on Hippocampal. Sport Physiology. Spring 2021; 13 (49): 199-222. Doi: 10.22089/spj.2020.9395.2065(In Persian).

[14] Ishrat T, Khan MB, Hoda MN, Yousuf S, Ahmad M, Ansari MA, et al. Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin in rats. Behavioural brain research. 2006;171(1):9-16. 10.1016/j.bbr.2006.03.009.

[15] Sodhi RK, Singh N. All-trans retinoic acid rescues memory deficits and neuropathological changes in mouse model of streptozotocin-induced dementia of Alzheimer's type. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2013;40:38-46. 10.1016/j.pnpbp.2012.09.012

[16] Calió ML, Mosini AC, Marinho DS, Salles GN, Massinhani FH, Ko GM, et al. Leptin enhances adult neurogenesis and reduces pathological features in a transgenic mouse model of Alzheimer’s disease. Neurobiology of disease. 2021;148:105219. 10.1016/j.nbd.2020.105219

[17] Yook JS, Rakwal R, Shibato J, Takahashi K, Koizumi H, Shima T, et al. Leptin in hippocampus mediates benefits of mild exercise by an antioxidant on neurogenesis and memory. Proceedings of the National Academy of Sciences. 2019;116(22):10988-93. 10.1073/pnas.1815197116

[18] Salehi OR, Hoseini A. The effects of endurance trainings on serum BDNF and insulin levels in streptozotocin-induced diabetic rats. Shefaye Khatam. 2017;5(2):52-61. (In Persian).10.18869/acadpub.shefa.5.2.52

[19] Marin Bosch B, Bringard A, Logrieco MG, Lauer E, Imobersteg N, Thomas A, et al. A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men. Scientific reports. 2021;11(1):14371. 10.1038/s41598-021-93813-5

[21] Murawska-Ciałowicz E, de Assis GG, Clemente FM, Feito Y, Stastny P, Zuwała-Jagiełło J, et al. Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test. Scientific reports. 2021;11(1):8599. 10.1038/s41598-021-88069-y

Volume 15, Issue 2 - Serial Number 96May 2023Pages 5-14

Volume 15, Issue 2 - Serial Number 96
May 2023
Pages 5-14