Abstract Background Posttraumatic stress disorder (PTSD) is a debilitating mental condition triggered by traumatic stress, and current treatments remain limited. Non-invasive phototherapy has shown promise in mood disorders, yet its efficacy in PTSD—particularly for early intervention and fear symptom mitigation—remains insufficiently explored. Objective This study aimed to investigate the preventive and therapeutic effects of blue non-invasive phototherapy (470 nm) on PTSD-related anxiety and fear behaviors in a rat model, focusing on neuronal activation and transcriptomic changes in emotion-related brain regions. Methods Sprague-Dawley (SD) rats (n = 100) were subjected to single inescapable electric foot shock after single prolonged stress procedure (SPS-S). Groups included control (Ctrl), SPS-S, SPS-S + immediate light therapy (SPS-S + I-LT), SPS-S + delayed light therapy (SPS-S + D-LT), and SPS-S + immediate and delayed light therapy combination (SPS-S + ID-LT). Behavioral assessments, including open field test (OFT), elevated plus maze (EPM) and fear conditioning, were conducted at week one and three post-intervention. Immunohistochemical staining for c-Fos expression and RNA sequencing of the medial prefrontal cortex (mPFC) were performed to evaluate neural activation and transcriptomic alterations. Results I-LT and ID-LT were associated with reduced anxiety-like behaviors in the OFT and EPM compared with untreated SPS-S-exposed rats (p < 0.001). Improvements in fear-related freezing behavior were observed at 3 weeks in the I-LT group and ID-LT group (p < 0.001), whereas D-LT was associated with anxiolytic effects without significant changes in fear responses. SPS-S exposure was associated with increased c-Fos expression in the infralimbic mPFC, and this elevation was attenuated in animals receiving I-LT or ID-LT. Transcriptomic analyses revealed stress-associated alterations in synapse-related pathways, which were modulated in the I-LT group. Selected synaptic genes were further examined by quantitative real-time PCR. Conclusions Blue light phototherapy produced distinct behavioral and molecular signatures in a rat model of traumatic stress. Immediate post-trauma intervention showed stronger associations with fear-related outcomes, supporting the potential relevance of early light-based interventions as a non-invasive adjunctive strategy for traumatic stress management.
Li et al. (Fri,) studied this question.