Objective: High-intensity exercise training effectively stimulates neurogenesis and neuroplasticity but may cause neurological exhaustion. This study investigated the combined effects of three recovery interventions—cold water immersion, LED light therapy, and branched-chain amino acid (BCAA) supplementation—on the expression of genes related to neurogenesis and neuroplasticity in the brain of male C57BL/6 mice following intense training.

Materials and Methods: Fifty-four C57BL/6J mice underwent 8-week treatments divided into nine groups (n=6 per group): control, high-intensity exercise alone, and exercise combined with various interventions including cold water, LED light therapy, BCAA supplementation, and their binary and ternary combinations. Gene expression was analyzed using bioinformatics approaches on microarray datasets, followed by validation of selected genes (FOS, ARC, BDNF, GRIN1, EGR1, and HOMER1a) using Real-Time PCR.

Findings: Bioinformatics analysis identified FOS, ARC, BDNF, GRIN1, EGR1, and HOMER1a as key regulators of neurogenesis and neuroplasticity. Intense training significantly decreased neurotrophic gene expression while elevating genes associated with neural stress. Notably, therapeutic interventions—particularly the triple combination—substantially modulated gene expression patterns, restoring them closer to control baseline levels.

Conclusion: The synergistic application of cold water immersion, LED light therapy, and BCAA supplementation effectively enhances the expression of neurotrophic and synaptoplasticity-related genes. These molecular changes represent a potential mechanism for facilitating neuronal regeneration and optimizing neural plasticity following high-intensity exercise stress.