Effects of Genetic Variation on the Efficacy of Aerobic Exercise
Study Details
Study Description
Brief Summary
This study investigates whether, after six weeks of exercise, a genetic variant (Val66Met) in the gene that makes a molecule (BDNF) important for brain health and function, influences the beneficial effects of a further session of exercise in sedentary, healthy males. The aim of this research is to determine whether not having this genetic variant (Val66Met) provides an advantage for achieving greater exercise-induced benefits. After six consecutive weeks of exercise (high-intensity interval training (HIIT), three times per week), the effects of a further session of exercise on brain activity are studied in healthy, sedentary males with and without the BDNF genetic variant. Further, whether the BDNF genetic variant impacts the effects of six weeks of aerobic exercise on blood BDNF levels, memory and cardiorespiratory fitness is examined. This data will help to understand whether genetic factors moderate the beneficial effects of exercise. Understanding what factors influence the effectiveness of exercise training programs is essential to individualize exercise programs and maximize their positive effects on the brain and during rehabilitation following brain injuries.
Condition or Disease | Intervention/Treatment | Phase |
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N/A |
Detailed Description
Aerobic exercise promotes brain health and function. Indeed, exercise has been shown to improve learning and memory, delay cognitive decline and protect against brain atrophy in healthy aging individuals. Additionally, exercise programs reduce brain injury and delay onset and progression of neurodegenerative diseases such as Alzheimer's. However, individual variability in the efficacy of these programs limit their widespread application as a "therapeutic". Genetic variants may contribute to the large degree of individual variability in the effects of exercise on cognition and brain health.
Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in activity-dependent neuroplasticity. Rodent studies show that increases in BDNF mediate the effects of exercise on learning and memory. A single nucleotide polymorphism in the BDNF gene that causes a valine (Val) to methionine (Met) substitution at codon 66 reduces activity-dependent secretion of BDNF and is associated with altered hippocampal activation and poorer episodic memory. The objective of this research is to determine whether after six consecutive weeks of high-intensity interval training (HIIT), three times per week, BDNF Val66Met polymorphism impacts the effects of a further HIIT session on corticospinal excitability as well as intracortical and spinal circuitry. Additionally, this study aims to assess whether BDNF Val66Met polymorphism moderates the effects of six consecutive weeks of HIIT on BDNF, working memory and cardiorespiratory fitness levels. The findings will indicate whether the BDNF Val allele provides an advantage for achieving greater exercise-induced benefits and could thus help individualize exercise programs to maximize their beneficial effects. These data will also provide insights into the mechanisms by which aerobic exercise induces neuroplasticity.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: V66V-HIIT Val/Val carriers who undergo high-intensity interval training (HIIT) for 6 weeks, 3 times per week |
Behavioral: High-Intensity Interval Training (HIIT)
Participants perform high-intensity interval training (HIIT) on a cycle ergometer. The HIIT protocol consists of a 3-minute warm-up at 50W, ten 60-second high-intensity cycling intervals interspersed with 90 seconds of active recovery at 30% of their peak power output and a 2-minute cool-down at 50W for a total of 17.5 minutes.
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Experimental: V66M-HIIT Val/Met carriers who undergo high-intensity interval training (HIIT) for 6 weeks, 3 times per week |
Behavioral: High-Intensity Interval Training (HIIT)
Participants perform high-intensity interval training (HIIT) on a cycle ergometer. The HIIT protocol consists of a 3-minute warm-up at 50W, ten 60-second high-intensity cycling intervals interspersed with 90 seconds of active recovery at 30% of their peak power output and a 2-minute cool-down at 50W for a total of 17.5 minutes.
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Outcome Measures
Primary Outcome Measures
- Corticospinal excitability [8 weeks]
Corticospinal excitability as measured by single-pulse TMS-evoked responses in a hand and forearm muscles.
- Intracortical circuits [8 weeks]
Intracortical circuits as measured by paired-pulse TMS-evoked responses in a hand muscle
- Spinal circuits [8 weeks]
Spinal circuits as measured by spinal Hoffman reflexes from a forearm muscle
- Blood BDNF [8 weeks]
Serum levels of BDNF as assessed by ELISA
Secondary Outcome Measures
- Cathepsin B [8 weeks]
Serum levels of cathepsin B as assessed by ELISA
- IGF-1 [8 weeks]
Serum levels of IGF-1 as assessed by ELISA
- VEGF [8 weeks]
Serum levels of VEGF as assessed by ELISA
- Osteocalcin [8 weeks]
Serum levels of osteocalcin as assessed by ELISA
- Working memory [8 weeks]
Working memory as assessed by the Automated Operation Span (OSPAN) Task
- Cardiorespiratory fitness [8 weeks]
Cardiorespiratory fitness as assessed by VO2 peak test
Eligibility Criteria
Criteria
Inclusion Criteria:
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do not engage or engage in less than or equal to 60 minutes of structured exercise per week (or two exercise sessions of 30 min/week; Heisz et al., 2017; Little et al. 2011) as per their self-report;
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must be able to engage in physical activity and thus must answer 'NO' to all questions on the Get Active Questionnaire (GAQ). If potential participants answer 'YES' to any of the GAQ questions, they are immediately deemed ineligible to partake in the research;
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must not take street drugs and medications, including alpha blockers, antibiotics, antipsychotics, benzodiazepines, beta-blockers, calcium channel blockers, systemic corticosteroids, muscle relaxants, neuromuscular blocking agents, sedatives, and psychostimulants, and must have no stable or unstable medical conditions, history of neurological or psychological disorders, head injury and/or surgery, seizures or have a family history of seizures or epilepsy, experience frequent headaches, migraines and sleep deprivation as per the TMS screening form;
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must be right-handed as per the handedness questionnaire;
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must be between 18 and 30 years old.
Exclusion Criteria:
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engage in more than 60 minutes of structured exercise per week (or two exercise sessions of 30 min/week; Heisz et al., 2017; Little et al. 2011) as per their self-report;
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are not able to engage in physical activity and thus answer 'YES' to any of the GAQ questions;
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take street drugs and medications, including alpha blockers, antibiotics, antipsychotics, benzodiazepines, beta-blockers, calcium channel blockers, systemic corticosteroids, muscle relaxants, neuromuscular blocking agents, sedatives, and psychostimulants, and must have no stable or unstable medical conditions, history of neurological or psychological disorders, head injury and/or surgery, seizures or have a family history of seizures or epilepsy, experience frequent headaches, migraines and sleep deprivation as per the TMS screening form;
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are not right-handed as per the handedness questionnaire;
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are younger than 18 years of age and older than 30 years of age.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | McMaster University, Ivor Wynne Centre (IWC) building | Hamilton | Ontario | Canada | L8S4K1 |
Sponsors and Collaborators
- McMaster University
Investigators
- Principal Investigator: Aimee Nelson, PhD, McMaster University
Study Documents (Full-Text)
None provided.More Information
Publications
- Begliuomini S, Casarosa E, Pluchino N, Lenzi E, Centofanti M, Freschi L, Pieri M, Genazzani AD, Luisi S, Genazzani AR. Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor. Hum Reprod. 2007 Apr;22(4):995-1002. Epub 2007 Jan 24.
- Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003 Mar;14(2):125-30.
- Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-69.
- Heisz JJ, Clark IB, Bonin K, Paolucci EM, Michalski B, Becker S, Fahnestock M. The Effects of Physical Exercise and Cognitive Training on Memory and Neurotrophic Factors. J Cogn Neurosci. 2017 Nov;29(11):1895-1907. doi: 10.1162/jocn_a_01164. Epub 2017 Jul 12.
- Itoh K, Hashimoto K, Kumakiri C, Shimizu E, Iyo M. Association between brain-derived neurotrophic factor 196 G/A polymorphism and personality traits in healthy subjects. Am J Med Genet B Neuropsychiatr Genet. 2004 Jan 1;124B(1):61-3.
- Lamy JC, Russmann H, Shamim EA, Meunier S, Hallett M. Paired associative stimulation induces change in presynaptic inhibition of Ia terminals in wrist flexors in humans. J Neurophysiol. 2010 Aug;104(2):755-64. doi: 10.1152/jn.00761.2009. Epub 2010 Jun 10.
- Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, Jung ME, Gibala MJ. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. J Appl Physiol (1985). 2011 Dec;111(6):1554-60. doi: 10.1152/japplphysiol.00921.2011. Epub 2011 Aug 25.
- Lommatzsch M, Zingler D, Schuhbaeck K, Schloetcke K, Zingler C, Schuff-Werner P, Virchow JC. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol Aging. 2005 Jan;26(1):115-23.
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- Lulic T, El-Sayes J, Fassett HJ, Nelson AJ. Physical activity levels determine exercise-induced changes in brain excitability. PLoS One. 2017 Mar 9;12(3):e0173672. doi: 10.1371/journal.pone.0173672. eCollection 2017.
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- Ozan E, Okur H, Eker C, Eker OD, Gönül AS, Akarsu N. The effect of depression, BDNF gene val66met polymorphism and gender on serum BDNF levels. Brain Res Bull. 2010 Jan 15;81(1):61-5. doi: 10.1016/j.brainresbull.2009.06.022.
- Phillips BE, Kelly BM, Lilja M, Ponce-González JG, Brogan RJ, Morris DL, Gustafsson T, Kraus WE, Atherton PJ, Vollaard NBJ, Rooyackers O, Timmons JA. A Practical and Time-Efficient High-Intensity Interval Training Program Modifies Cardio-Metabolic Risk Factors in Adults with Risk Factors for Type II Diabetes. Front Endocrinol (Lausanne). 2017 Sep 8;8:229. doi: 10.3389/fendo.2017.00229. eCollection 2017.
- Rovio S, Kåreholt I, Helkala EL, Viitanen M, Winblad B, Tuomilehto J, Soininen H, Nissinen A, Kivipelto M. Leisure-time physical activity at midlife and the risk of dementia and Alzheimer's disease. Lancet Neurol. 2005 Nov;4(11):705-11.
- Schinder AF, Poo M. The neurotrophin hypothesis for synaptic plasticity. Trends Neurosci. 2000 Dec;23(12):639-45. Review.
- Teri L, Gibbons LE, McCurry SM, Logsdon RG, Buchner DM, Barlow WE, Kukull WA, LaCroix AZ, McCormick W, Larson EB. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA. 2003 Oct 15;290(15):2015-22.
- Unsworth N, Heitz RP, Schrock JC, Engle RW. An automated version of the operation span task. Behav Res Methods. 2005 Aug;37(3):498-505.
- Vaynman S, Ying Z, Gomez-Pinilla F. Hippocampal BDNF mediates the efficacy of exercise on synaptic plasticity and cognition. Eur J Neurosci. 2004 Nov;20(10):2580-90.
- Weuve J, Kang JH, Manson JE, Breteler MM, Ware JH, Grodstein F. Physical activity, including walking, and cognitive function in older women. JAMA. 2004 Sep 22;292(12):1454-61.
- BDNF V66M Exercise Study