Exercise and the Brain: What BDNF Does to Neurons

For a long time it was thought that neurons were cells that could not be regrown. This turned out to be wrong. The nervous system retains neuroplasticity throughout life, and physical activity is one of its most powerful activators. The key mediator of this process is the protein BDNF.

What BDNF Is and What It Does in the Brain

BDNF (brain-derived neurotrophic factor) is a protein from the neurotrophin family. It supports the survival of existing neurons, stimulates the formation of new ones in the hippocampus (neurogenesis), and enhances synaptic plasticity — the ability of neurons to change the strength of their connections with one another. It is precisely through synaptic plasticity that memories are formed, consolidated, and updated.

The hippocampus — a structure critical for spatial navigation and declarative memory — is especially rich in BDNF receptors. With age its volume gradually decreases: in most people this process begins after 40 and accelerates with a sedentary lifestyle. Lower blood BDNF levels are associated with cognitive decline and an increased risk of neurodegenerative disease.

How Exercise Changes BDNF Levels: Data from 35 RCTs

The systematic review and meta-analysis by Gholami, Mesrabadi, Iranpour, and Donyaei (Experimental Gerontology, 2025) pooled 35 randomized controlled trials in older adults. The result: exercise reliably raises resting BDNF levels — pooled effect SMD = 0.56 (95% CI: 0.28–0.85), corresponding to a moderate evidence-based effect size.

Among modalities, resistance training showed the greatest increase (SMD = 0.76), followed by combined (aerobic + resistance) programs (SMD = 0.55) and aerobic training alone (SMD = 0.48). Moderate-to-high intensity yielded an effect of SMD = 0.83 — higher than moderate intensity alone. A frequency of 3–4 sessions per week proved more effective than 1–2 per week.

Aerobic Training Increases Hippocampal Volume: RCT Evidence

The most-cited direct evidence is the randomized controlled trial by Erickson et al. (PNAS, 2011). 120 older adults were randomly assigned to an aerobic training group (walking three times per week for 12 months, with load progressively increasing to 40 minutes) or a stretching group. MRI before and after: in the aerobic group, hippocampal volume grew by 2.12% (left) and 1.97% (right). In the stretching group, volume continued to decline. The authors calculated that the gain corresponded to reversing approximately two years of age-related hippocampal atrophy.

It is important to understand: this is an observed association within a single RCT, not a universal effect across all ages and populations. Nevertheless, it is a direct RCT with MRI measurements — not a questionnaire — and the effect has been reproduced in subsequent meta-analyses of aerobic interventions in older adults.

Why Resistance Training Unexpectedly Takes the Lead

In popular thinking, "exercise for the brain" means aerobic activity: running, cycling, swimming. The data from Gholami et al. (2025) challenge this assumption: resistance training produced the greatest BDNF increase of all modalities (SMD = 0.76 versus 0.48 for aerobic). The mechanism is likely linked to neuromuscular system engagement and other biochemical cascades (IGF-1, irisin) that additionally stimulate the neurotrophic response. The data were obtained in older adults; extrapolation to other age groups warrants caution, but the trend is consistent.

The Regimen That Works

According to the meta-analysis, the most effective interventions shared three common parameters: duration of at least 12 weeks, moderate-to-high intensity (not merely moderate), and a frequency of 3–4 sessions per week. None of these thresholds looks unattainable — this is the normal routine of a regularly training person, not the protocol of an elite athlete.

An additional nuance: an acute BDNF spike occurs immediately after each workout, but a sustained elevation of the resting baseline level requires regular multi-week training. One intense month followed by a long break will not produce the same adaptation as a consistent routine.