Peripheral mechanisms

inducing neurogenesis, hippocampal function and mental health in children: The role of exercise.

SaludmentalenniñosIEmerging evidence suggests that exercise leads to an increase in brain-derived neurotrophic factor (BDNF) in the central nervous system to promote improvement in cognition, anxiety and depression. However, mechanisms whereby exercise has a positive influence on brain, cognition and mental health are unknown. Recent animal studies have identified peripheral mechanisms potentially stimulated by exercise that could increase BDNF levels in brain which in turn may be related with higher neurogenesis and synaptogenesis mainly in the hippocampus and with better hippocampal-dependent mood, learning, and memory. Peripheral factors induced by exercise and candidates to increase BDNF levels in the hippocampus are: FNDC5-irisin, fibronectin type III domain–containing protein 5 that is released into the circulation as Irisin; BHB, B-hydroxybutyrate; and CTSB, Cathepsin B. However, available evidence comes from animal models. The radical novelty of the present proposal is to test whether these peripheral mechanisms are induced by exercise in humans. This study is risky, due to the complex methodology to determine some of those factors in blood, specially irisin, but ambitious as it has the potential of resulting in a major scientific breakthrough in this field.

This project is cost-effective and realistic to carry out during the 2 years of the project, which is possible thanks to a previous investment, the ActiveBrains randomized controlled trial. Specifically, we will use frozen biological samples, magnetic resonance images, and cognitive and mental health tests assessed before and after a 20weeks exercise program in 100 overweight/obesity children aged 8-11 years. The aim of this project is to examine novel peripheral factors that induce the effects of exercise on BDNF, neurogenesis and hippocampal function and mental health. This Innovative Project Grants «Explora Ciencia» could give us the opportunity to explore for the first time these peripheral mechanisms in human.

Graphical illustration of the Aims and hypothesis of the current project
Figura 1 mecanismos
Study design
Figura 2 mecanismos


Collecting blood samples.


The Spanish Ministry of Economy and Competitiveness (DEP2017-91544-EXP) and the Alicia Koplowitz Foundation (ALICIAK-2018). The present study is also part of the ActiveBrains project, which was funded by the Spanish Ministry of Economy and Competitiveness and the “Fondo Europeo de Desarrollo Regional (FEDER)” with the following reference number: DEP-2013-47540.


the publications of the “Peripheral mechanisms inducing neurogenesis, hippocampal function and mental health in children: The role of exercise” are now available at the ActiveBrains website.