👤 Tõnis Timmusk

Physical exercise and nutritional strategies have become powerful tools for improving brain health, boosting cognitive performance, slowing cognitive decline, and reducing the risk of neurodegenerative diseases, primarily by influencing neurotrophic factors such as brain-derived neurotrophic factor (BDNF). This review examines the impact of various exercise types (endurance, high-intensity interval training, and resistance) along with dietary approaches (ketogenic diet and intermittent fasting) on BDNF, with a focus on their potential to promote cognition and neuroprotective benefits, particularly in the middle-aged and older population. Several molecular and physiological pathways may be involved, including activation of the PGC-1α-FNDC5-BDNF pathway, lactate signaling, increased blood flow to the brain and body, splenic platelet release, and stimulation of TrkB, IGF-1, irisin, and cathepsin B. Nutritional interventions may also boost BDNF through mechanisms involving β-HB and Notch 1 signaling. Research from both animal and human studies highlights the potential benefits of exercise and dietary modifications in supporting brain health and cognitive function. However, differences in study design and methodological limitations make it difficult to draw firm conclusions. These effects appear to be influenced by factors such as exercise characteristics (intensity, modality, and duration), the timing of blood collection, and the type of cognitive assessments. Future studies should focus on identifying the most effective intervention protocols and mechanisms, as well as understanding the individual factors that influence responsiveness to neurotrophic changes. Overall, targeted exercise and dietary strategies offer a promising approach to maintain brain health and reduce cognitive decline associated with aging and disease. Show less

Brain-derived neurotrophic factor (BDNF) is a neurotrophin with crucial roles in the developing and adult nervous system, contributing to neuronal survival, differentiation, and synaptic plasticity. The pleiotropic functions of BDNF require stringent spatiotemporal control of its expression, making BDNF one of the most thoroughly studied activity-regulated genes. Over the years, substantial evidence has accumulated, providing insights into BDNF gene structure, numerous mRNA variants, their different localization patterns and translational efficiencies, as well as the functions of the BDNF protein in different tissues. This review aims to summarize the current understanding of the mechanisms governing BDNF expression at transcriptional, posttranscriptional, and translational levels, offering an integrated perspective of BDNF regulation. Show less