Physical exercise as a modulator of BDNF expression: a systematic review with meta-analysis and meta- regression.

• Grant number: 25/28041-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: March 02, 2026
• End date: April 01, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Lucas Melo Neves
• Grantee: Fernanda Pereira Lemos Barbosa
• Supervisor: Emerson Sebastiao
• Host Institution: Universidade de Santo Amaro (UNISA). São Paulo , SP, Brazil
• Institution abroad: University of Illinois at Urbana-Champaign, United States
• Associated to the scholarship: 24/15308-5 - THE IMPACT OF PHYSICAL ACTIVITY INDICATORS ON BRAIN ASYMMETRY: A MAGNETIC RESONANCE STUDY, BP.IC

Abstract

Introduction: Physical exercise is associated with improved brain health, and this effect appears to be mediated by alterations in neurotrophic and inflammatory markers. Exercise also promotes neuronal plasticity, enhances cell survival, and contributes to better cognitive performance. Among the molecules involved in these processes, brain-derived neurotrophic factor (BDNF) plays a major role due to its functions in neurogenesis and neuronal activity regulation. Previous evidence, such as the study by Tsai et al. (2018), has shown that even a single 30-minute session of aerobic exercise can significantly increase serum BDNF levels. Rationale: Current evidence suggests that physical exercise interventions have the potential to modulate BDNF release and, consequently, support brain health. In preliminary searches, we identified five recent systematic reviews with meta-analyses addressing this topic (Behrad et al., 2024; Fleitas et al., 2022; Gholami et al., 2025; Titus et al., 2021; Wang et al., 2022). Although each review offers relevant contributions, they also present methodological differences and limitations that justify the development of a new, more comprehensive synthesis. Aims: To conduct a systematic review with meta-analysis of human studies across all age groups that investigated the effects of physical exercise on BDNF modulation. Additionally, to perform meta-regression analyses to identify factors that may influence the magnitude of this modulation. Methods: This study will follow methodological standards for systematic reviews and meta-analyses in medical research, including the 24-step guideline for review preparation. Searches will be performed in the PubMed, Web of Science, Embase, EBSCO SportDiscus, and PsycInfo databases. Reference management and study selection will be conducted using EndNote and Rayyan. Analysis of the results: Data synthesis will be conduted using the Comprehensive Meta-Analysis software (version 4.1). Heterogeneity will be evaluated through the I² statistic, and potential publication bias will be examined through visual inspection of funnel plots.Keywords: Physical exercise; Elderly; Children; Adults; Youth; BDNF. (AU)