Transcranial near infrared therapy reprograms metabolism to rescue sleep and place cell functionality.

Sleep disturbances exacerbate Alzheimer's disease (AD) pathology, accelerating cognitive decline and impairing hippocampal memory functions. This study explores the therapeutic potential of transcranial near-infrared (tNIR) therapy in mitigating hippocampal dysfunction caused by chronic sleep deprivation (SD) in a tauopathy mouse model of AD. Using targeted 808 nm tNIR therapy, we observed restored cerebral blood flow, enhanced metabolic reprogramming favoring oxidative phosphorylation, and reestablished ionic homeostasis. These effects improved hippocampal oscillatory dynamics, including enhanced theta, gamma, and delta power, synchronized sharp-wave ripples (SWRs), and improved the phase-locking of place cell activity to theta and awake SWR oscillations. tNIR therapy also refined spatial encoding precision and reorganized sleep architecture, promoting slow-wave sleep while reducing REM disturbances. These findings position tNIR therapy as a promising non-invasive approach for addressing SD-driven cognitive and neural impairments, offering a novel intervention for sleep-related neurodegeneration in AD.