Photobiomodulation therapy mitigates depressive-like behaviors by remodeling synaptic links and mitochondrial function.

Depression, a multifactorial mental disorder, characterized by cognitive slowing, anxiety, and impaired cognitive function, imposes a significant burden on public health. Photobiomodulation (PBM), involving exposure to sunlight or artificial light at a specific intensity and wavelength for a determined duration, influences brain activity, functional connectivity, and plasticity. It is recognized for its therapeutic efficacy in treating depression, yet its molecular and cellular underpinnings remain obscure. Here, we investigated the impact of PBM with 468 nm light on depression-like behavior and neuronal damage in the chronic unpredictable mild stress (CUMS) murine model, a commonly employed animal model for studying depression. Our results demonstrate that PBM treatment ameliorated behavioral deficits, inhibited neuroinflammation and apoptosis, and notably rejuvenates the hippocampal synaptic function in depressed mice, which may be mainly attributed to the up-regulation of brain-derived neurotrophic factor signaling pathways. In addition, in vitro experiments with a corticosterone-induced hippocampal neuron injury model demonstrate reduced oxidative stress and improved mitochondrial function, further validating the therapeutic potential of PBM. In summary, these findings suggest PBM as a promising, non-invasive treatment for depression, offering insights into its biological mechanisms and potential for clinical application.