Effects of transcranial photobiomodulation on peripheral biomarkers associated with oxidative stress and complex IV activity in the prefrontal cortex in rats subjected to chronic mild stress

This study addresses the need for effective alternatives to treat major depressive disorder (MDD) in patients who do not respond to conventional therapies. Transcranial photobiomodulation therapy (tPBM) shows promise by enhancing mitochondrial function and reducing oxidative stress, as demonstrated in the chronic mild stress (CMS) rat model. This study aimed to analyze the impact of tPBM with two wavelengths (red and infrared) on behavioral and biological parameters related to MDD in a CMS model. Male rats were subjected to CMS for five weeks and categorized into resilient and susceptible groups using the sucrose consumption test. The CMS-S group received tPBM treatment (600nm and 840nm) for five weeks. Biological measures included lipid damage (TBARS), antioxidant defense (TEAC), mitochondrial complex IV activity (CCO), and nitric oxide (NO) concentration in the prefrontal cortex and blood. Post-tPBM treatment (both red and infrared groups) exhibited increased sucrose consumption compared to the sham (Kruskal-Wallis chi-squared=26.131; p<0.001). Both groups presented higher serum TEAC levels than the sham and control groups, although these effects were not statistically significant (p=0.306). The red group showed lower peripheral TBARS levels (M=9.50, SD=2.87) than the sham group (M=13.66, SD=2.20, p=0.0048). The infrared group showed higher NO levels in the hippocampus than the sham group (Mean=107.83, SD=6.48, Dunn-Test p=0.0134) and higher prefrontal CCO activity levels than the red group (p=0.012). This study demonstrated that tPBM using both wavelengths significantly improved behavioral and biological parameters in the CMS rat model, suggesting potential therapeutic benefits for MDD by ameliorating oxidative stress and enhancing mitochondrial function.