Hydrogen-Mediated Activation of the Nrf2/HO-1 Signaling Pathway Improves Cognitive Impairment in Sleep-Deprived Mice

This study investigated the effects of hydrogen (H₂) on cognitive impairment in sleep-deprived mice mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.

A chronic sleep deprivation (SD) model was established using the modified multiple platform method, with 18 h of deprivation daily for 28 consecutive days. Cognitive function was evaluated using the Morris water maze and novel object recognition (NOR) test. Histopathological and biochemical analyses, including hematoxylin and eosin staining, Nissl staining, immunohistochemistry, and enzyme-linked immunosorbent assay, were performed to assess oxidative stress and inflammation-related markers.

The results demonstrated that H₂-treated mice showed significantly shorter escape latency, longer target quadrant duration, and higher NOR index compared to controls. Concurrently, Nrf2/HO-1 expression was significantly upregulated, while interleukin-1β and tumor necrosis factor-alpha levels were reduced. Additionally, glutathione peroxidase and superoxide dismutase activities were restored.

These results indicate that H₂ alleviates oxidative stress and neuroinflammation through Nrf2/HO-1 pathway activation, mitigating SD-induced cognitive impairment. This research provides a theoretical foundation for potential clinical applications.