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

## TL;DR

Hydrogen improves cognitive function in sleep-deprived mice by reducing oxidative stress and inflammation through the Nrf2/HO-1 pathway.

## Contribution

This study demonstrates hydrogen's novel role in mitigating sleep deprivation-induced cognitive impairment via Nrf2/HO-1 pathway activation.

## Key findings

- Hydrogen-treated mice showed improved cognitive performance in memory and recognition tests.
- Hydrogen upregulated Nrf2/HO-1 signaling and reduced inflammatory markers like IL-1β and TNF-α.
- Hydrogen restored antioxidant enzyme activities such as glutathione peroxidase and superoxide dismutase.

## Abstract

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.

Hydrogen enhances memory and learning capabilities in sleep‐deprived mice by activating the Nrf2/HO‐1 signaling pathway, while suppressing neuronal damage, oxidative stress, and inflammatory responses.