The Impact of High-Intensity Interval Training on Brain Derived Neurotrophic Factor in Brain: A Mini-Review

Abstract

The brain-derived neurotrophic factor (BDNF) is a protein mainly synthetized in the neurons. Early evidence showed that BDNF participates in cognitive processes as measured at the hippocampus. This neurotrophin is as a reliable marker of brain function; moreover, recent studies have demonstrated that BDNF participates in physiological processes such as glucose homeostasis and lipid metabolism. The BDNF has been also studied using the exercise paradigm to determine its response to different exercise modalities; therefore, BDNF is considered a new member of the exercise-related molecules. The high-intensity interval training (HIIT) is an exercise protocol characterized by low work volume performed at a high intensity [i.e., ≥80% of maximal heart rate (HRmax)]. Recent evidence supports the contention that HIIT elicits higher fat oxidation in skeletal muscle than other forms of exercise. Similarly, HIIT is a good stimulus to increase maximal oxygen uptake (VO₂max). Few studies have investigated the impact of HIIT on the BDNF response. The present work summarizes the effects of acute and long-term HIIT on BDNF.

Keywords: brain; brain-derived neurotrophic factor; health; high-intensity interval training; physical exercise.

FIGURE 1

(A) Moderate-intensity continuous training (MICT) increases intracellular calcium (Ca²⁺) levels in neurons through the NMDA receptor. Intracellular Ca²⁺ increases the activity of calmodulin dependent kinase II (CaMKII), triggering the activation of the MAPK/ERK/MSK cascade signaling, resulting in the increase of the expression and phosphorylation of cAMP response element-binding protein (CREB). Finally, CREB enhance the Bdnf transcription. This molecular mechanism described above result in a higher BDNF protein, the neurotrophin is released by the neuron to induce transcription of cognitive genes. The present model is based on Gomez-Pinilla’s studies (Fernandes et al., 2017). (B) MICT enhances the mitochondrial activity in neurons. Higher mitochondrial activity increases reactive oxygen species (ROS) from complexes I and III. The change in ROS levels modify and regulate a wide of signaling process including the CREB-BDNF signaling pathway. Once activated, BDNF regulates a positive feedback mechanism to induce the cognitive genes transcription. Additionally, the aerobic exercise increases the calcium concentration in neurons; this ion through the calpain and xanthine oxidase increases the ROS that consequently increase the CREB’s activation and Bdnf expression. (C) Exercise performed at high intensity (≥80% HRmax) activates several metabolic pathways in muscle (including glycolysis), this condition generates a higher systemic blood lactate concentration reaching the brain, this metabolite can be oxidized by astrocytes or neurons to produce glucose (Dienel and Hertz, 2001). In addition, experimental evidence indicates that lactate increase NMDA activity and intracellular Ca²⁺ levels in neurons. Indeed, it is possible that the lactate in neurons enhance the CaMKII activity and the MAPK/ERK/MSK signaling to induce the CREB’s activation and Bdnf expression. Finally, the BDNF activate a positive loop to induce the expression of cognitive genes (Yang J. et al., 2014).

FIGURE 2

Mechanism proposed about the High Intensity Interval Training (HIIT) impact on BDNF synthesis in brain. (A) HIIT increases mitochondrial activity (not reported) and ROS concentration in neurons (Afzalpour et al., 2015) compared with MICT. ROS induce higher Creb-Bdnf transcription and signaling than MICT (not reported). (B) HIIT causes greater Ca²⁺ concentration in neurons than MICT (not reported); this condition enhances the CaMKII activity and MAPK/ERK/MSK signaling to activate the Creb-Bdnf transcription and neuronal plasticity. Additionally, the intracellular calcium can increase the ROS generation in neurons. Once synthetized, ROS can activate Creb-Bdnf transcription. Currently, there is not experimental evidence to indicate that HIIT triggers more this mechanism than MICT. (C) HIIT elevate systemic blood lactate concentration, and consequently enhance the NMDA receptor activity to increase intracellular Ca²⁺ concentration in neurons (not reported). The ion activates the CaMKII activity and MAPK/ERK/MSK signaling to induce the Creb-Bdnf transcription and neuronal plasticity (not reported). (?): not reported.