The effects of aerobic exercise intensity and duration on levels of brain-derived neurotrophic factor in healthy men.

Author:Schmolesky, Matthew T.
Position::Research article - Report


Brain-derived neurotrophic factor (BDNF) has been recognized as an important tropic hormone in the regulation of neuron morphology and survival. Endogenous BDNF is known to be involved in cellular development and growth, mood regulation, and cognitive functions such as learning and memory. Low circulating BDNF levels have been associated with a wide range of neuropsychiatric disorders including depression (Karege et al., 2002), bipolar disorder (Cunha et al., 2006), schizophrenia (Zhang et al., 2007) and neurodegenerative diseases (Yu et al., 2008), although no causal relationship has yet been established. Research over the past decade has investigated the factors that can acutely and chronically elevate brain levels of BDNF in animals and circulating levels of BDNF in humans, based on the assumption that elevated BDNF levels can lead to improved brain health.

Research has consistently shown that chronic aerobic exercise can elevate baseline BDNF levels in the hippocampus, striatum, and various cortical regions in laboratory animals (Ding et al., 2004; Neeper et al., 1996; Oliff et al., 1998; Rasmussen et al., 2009; Vaynman et al., 2004a; Widenfalk et al., 1999), and Suijo et al. (2013) have recently demonstrated that resistance exercise can also elevate BDNF levels in the hippocampus. Encouragingly, BDNF transcription can be induced in the rat hippocampus after only three consecutive days of aerobic exercise. Also, unlike other neurotrophic factors which showed tolerance to chronic exercise, BDNF levels remained upregulated in the rat hippocampus after 28 consecutive days of wheel running (Molteni et al., 2002). In animal models of disease, chronic exercise has provided BDNF benefits such as cell survival (Ang et al., 2003), decreased depressive symptoms (Marais et al., 2009), and cellular protection and functional recovery after traumatic brain injury (Griesbach et al., 2004). Furthermore, chronic aerobic exercise seems to have a robust effect on cognition, as various intensities and durations of voluntary and forced exercise have consistently improved learning and memory in healthy laboratory animals, whether assessed by Morris water maze (Adlard et al., 2004; Huang et al., 2006; Vaynman et al., 2004b), radial arm maze (Anderson et al., 2000), Y-maze (Van der Borght et al., 2007), object recognition tasks (O'Callaghan et al., 2007), or pain avoidance training (Liu et al., 2008; Radak et al., 2006). In each of these studies, an increase in BDNF mRNA or protein levels was positively associated with performance enhancement.

In humans, chronic aerobic exercise has been tested for its ability to raise baseline circulating BDNF levels. Several chronic exercise studies suggest that aerobic training can increase resting levels of circulating BDNF (Seifert et al., 2010; Zoladz et al., 2008). However, the majority of chronic exercise studies, especially those not using aerobic exercise training, have not observed increased basal circulating BDNF levels (Goekint et al., 2010; Griffin et al., 2011; Levinger et al., 2008; Schiffer et al., 2009).

While the impact of chronic exercise on BDNF has been extensively tested, particularly in animal studies, much less is known about the effects of a single bout of aerobic exercise on brain BDNF levels. Several animal studies have demonstrated significantly increased BDNF mRNA levels in the rat hippocampus after a single bout of six hours voluntary wheel running (Chen and Russo-Neustadt, 2009; Oliff et al., 1998). Huang et al., (2006) also reported a strong BDNF response in the hippocampus (~50% increase) of rodents after a single bout of aerobic exercise, with no difference between moderate or intense exercise. However, Klintsova et al. (2004) did not find an effect of acute moderate intensity aerobic exercise on BDNF levels in the cerebellum or motor cortex of rats; BDNF levels were elevated in the cerebellum only after five days of training and in the motor cortex after 14 days.

Human research investigating the effect of acute single-bout aerobic exercise has focused on two areas in particular, either characterizing the change in serum BDNF (sBDNF) levels after one exercise session, or identifying the effects of exercise intensity on these post-exercise sBDNF levels. The acute effect of exercise on human sBDNF levels is characterized as a transient, moderate (~20-40%) increase (Gold et al., 2003; Rojas Vega et al., 2006; Tang et al., 2008). Serum BDNF levels rise during aerobic exercise, and quickly return to baseline levels upon exercise cessation, approximately 10-15 minutes after exercise offset (Rojas Vega et al., 2006; Tang et al., 2008). High intensity exhaustive aerobic exercise for a short duration (Rojas Vega et al., 2006), or sustained moderate intensity exercise (Gold et al., 2003) appear sufficient to increase sBDNF levels. Encouragingly, as little as 15 minutes of moderate intensity exercise has significantly elevated sBDNF levels in healthy human subjects (Tang et al., 2008). Ferris et al. (2007) clearly demonstrated an effect of aerobic exercise intensity on sBDNF levels using a within subjects counterbalanced design. Their report suggested that low intensity exercise was insufficient to elevate BDNF levels relative to baseline, while high intensity exercise for a comparable duration significantly elevated sBDNF levels (Ferris et al., 2007).

Human studies to date have not systematically varied exercise duration across acute aerobic conditions, and only several studies have examined the impact of exercise intensity. Therefore, the present study was designed to assess for the first time the combined effects of exercise intensity and duration on sBDNF levels in young healthy adult humans and to assess the extent to which sBDNF levels can be elevated in relation to sedentary controls.



Healthy adult males aged 18-25 years were recruited from introductory psychology courses at Weber State University through informational postings and classroom announcements. This study was limited to male subjects to reduce variability in BDNF levels that vary across gender and vary with menstrual cycle status in females (e.g. Begliuomini et al., 2007). A follow-up study is currently underway to assess the impact of physical exercise on BDNF in women, while accounting for menstrual cycle status and estrogen levels. All postings and announcements contained information regarding the experimental procedure, exclusion criteria, instructions for dress and eating schedules, as well as times and meeting locations. Participant recruitment and experimental procedures were approved by an IRB committee and were implemented in accordance with the Declaration of Helsinki. Prior to participation, subjects were required to complete an informed consent document, emergency contacts form, demographics survey, and an exercise readiness assessment (a modified version of the Physical Activity Readiness Questionnaire or PAR-Q published by the American College of Sports Medicine). The exercise readiness assessment was reviewed just prior to exercise; subjects' responses were used to determine qualification for the study, and to identify subjects with medical contraindications to exercise. Participant exclusions based on self report included: past or present cardio-pulmonary diseases or joint or muscle disease, current tendon or bone damage, metabolic disease, blood borne pathogens, symptoms of illness, or noncompliance with the request to abstain from eating and consuming caffeinated beverages 2 hours prior to the study.

Subjects provided information on their average weekly exercise patterns via self-report, first by estimating the "number of hours exercised in the past week" and the "average number of hours exercised, per week, over the past six months," and then by listing the average number of hours attributed to individual sports or physical routines (e.g. basketball, cycling, martial arts, soccer, swimming, weight lifting, etc.). Subjects were asked to correct discrepancies between the initial overall estimate and the more detailed sport/routine estimates. Regular exercise patterns played no role in subject recruitment and, as expected, the final subject pool included those that exercised regularly and those that did not.

During study sessions, 50 subjects were randomly assigned to one of six exercise conditions based on exercise intensity (vigorous, moderate, or sedentary control), and duration (20 or 40 min), using quota sampling. Conditions are referred to as Vig20, Vig40, Mod20, Mod40, Con20, and Con40, respectively.

Participants were asked to exercise at the proper intensity and durations of exercise. Subject data were not included without proper adherence to assigned exercise conditions. Three subjects were excluded due to incorrect completion of exercise condition (one from Vig20, two from Mod20). Additional subjects were recruited to meet quota sampling. Baseline sBDNF levels are known to be extremely variable in the human population (Knaepen et al., 2010). To reduce the impact of outliers, subject data were excluded from the reported analyses if the baseline sBDNF level was [greater than or equal to] the 99th percentile, or [less than or equal to] the 1st percentile (i.e. 2.33 S.D. above or below the mean baseline sBDNF, n = 47). Two subjects were excluded from the Mod20 condition due to elevated baseline sBDNF levels. Final sample sizes per condition were as follows: Vig20 n = 9, Vig40 n = 9, Mod20 n= 9, Mod40 n = 8, Con20 n = 5, Con40 n = 5.

Exercise Conditions

All study sessions were carried out between 14:00 and 18:00 hours to limit circadian and other time-of-day effects on sBDNF levels. All data collection was conducted with ambient temperature at 22[degrees]C and normal humidity.

Vigorous (80% heart rate reserve) and moderate (60% heart rate reserve) exercise was carried out on cycle ergometers (Life Fitness LifeCycle 9100, Schiller Park, IL, USA) in the...

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