Transcranial Photobiomodulation Modulates Oxidative Stress Biomarkers and Complex IV Activity in Anhedonic-Like Behavior

Major depressive disorder (MDD) is a prevalent and complex condition with limited treatment success in many patients. Photobiomodulation (PBM), particularly transcranial PBM (tPBM) using red to near-infrared light, has emerged as a promising non-invasive intervention. However, optimal parameters and precise mechanisms remain unclear. This research aimed to analyze the effects of transcranial photobiomodulation (red and infrared) on behavioral and biological parameters related to MDD in a chronic mild stress (CMS) model. Male Wistar rats were exposed to CMS for five weeks and subsequently categorized into two groups-resilient (CMS-R) and susceptible (CMS-S)-based on their performance in the sucrose consumption test (SCT). The CMS-S group was further divided into three subgroups: (1) sham treatment, (2) tPBM red (600 nm), and (3) tPBM infrared (840 nm). A control group of non-stressed animals was included for baseline comparisons. 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 were measured. As expected, post-tPBM treatment (both red and infrared groups) exhibited increased sucrose consumption compared to the sham (p < 0.001). The red and infrared presented higher serum TEAC levels than the sham and control groups, but these effects did not reach statistical significance (p = 0.306). In contrast, the red group showed lower peripheral TBARS levels than the sham group (p = 0.0048); such effect was similar to the control non-stress group. The infrared group showed higher NO levels within the hippocampus than the sham group p = 0.0134) and higher prefrontal CCO activity levels than the red group (p = 0.012), which was similar to the control non-stress group. Our study demonstrated that animals treated with tPBM using red (600 nm) or infrared (840 nm) wavelengths exhibited significant improvements in both behavioral and biological parameters in the CMS model. In particular, tPBM may offer therapeutic benefits by ameliorating oxidative stress and enhancing mitochondrial function, thereby presenting a promising alternative for the management of MDD.