Photobiomodulation attenuates corticosterone-induced neuronal injury via activation of the AMPK/ULK1 signaling pathway.

Corticosterone (CORT)-induced neuronal injury represents a key pathological basis of stress-related neuropsychiatric disorders and is closely associated with mitochondrial dysfunction and impaired autophagic flux. Photobiomodulation (PBM), a non-invasive light-based neuromodulatory approach, has shown neuroprotective effects in various experimental models. However, whether its protective actions are associated with AMP-activated protein kinase (AMPK)-mediated regulation of autophagy remains to be established. CORT exposure was used to establish an in vitro neuronal injury model in HT22 cells. The optimal irradiation parameters of 808 nm PBM were first determined, and its protective effects were subsequently evaluated by assessing cell viability, oxidative status, inflammatory activity, mitochondrial function, and apoptosis. To further investigate the underlying mechanism, the AMPK inhibitor Compound C was employed. PBM significantly improved cell viability, attenuated oxidative stress and neuroinflammation, restored mitochondrial function, and suppressed apoptosis in CORT-treated cells. Mechanistically, PBM reversed the CORT-induced reduction in AMPK and UNC-51-like kinase 1 (ULK1) phosphorylation, increased the LC3-II/I ratio, reduced p62 accumulation, and was associated with improved autophagy-related activity. Importantly, these protective effects were largely attenuated by pharmacological inhibition of AMPK with Compound C, supporting a critical role for AMPK signaling in PBM-mediated neuroprotection. Collectively, the results demonstrate that 808 nm PBM protects neurons against CORT-induced injury through mechanisms involving restoration of mitochondrial homeostasis and activation of AMPK-ULK1 signaling, accompanied by evidence of improved autophagy-related function. The present study advances our understanding of the neuroprotective mechanisms of PBM and provides experimental support for its further investigation as a non-pharmacological intervention for stress-related neuronal injury and associated neuropsychiatric disorders.