Hydrogen Gas Protects Brain Cells in Alzheimer's Disease Mice
- Authors
- Chaodeng Mo, Johny Bajgai, Md Habibur Rahman, Hui Ma, Thu Thao Pham, Haiyang Zhang, Buchan Cao, Eun-Sook Jeong, Cheol-Su Kim, Kyu-Jae Lee
- Journal
- Antioxidants
- Year
- 2026
- DOI
- 10.3390/antiox15030404
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- South Korea
- Health Condition
- Alzheimer's Disease
- Body System
- Nervous System
TL;DR
Hydrogen inhalation reduced oxidative stress, inflammation, and amyloid burden while improving mitochondrial function in a 5xFAD mouse model of Alzheimer’s disease.
Key Finding
Hydrogen gas inhalation reduced oxidative stress and inflammation while decreasing amyloid-beta accumulation in the brains of mice genetically engineered to develop Alzheimer's-like pathology.
Summary
Researchers tested whether breathing hydrogen gas could help mice with an Alzheimer's-like disease. The mice that breathed 2% hydrogen for one hour daily over four weeks showed reduced brain damage markers, lower inflammation in their blood, better energy production in brain cells, and less buildup of amyloid-beta (a protein linked to Alzheimer's). The hydrogen appeared to work by reducing harmful molecules called free radicals and calming the immune system in the brain.
Practical Takeaway
This mouse study provides early evidence that hydrogen gas may have neuroprotective properties relevant to Alzheimer's disease, but it is not yet clear whether these results would apply to humans. Much more research, including human clinical trials, would be needed before hydrogen therapy could be considered a treatment option for neurodegenerative diseases.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which amyloid-beta (Aβ) accumulation, oxidative stress (OS), and chronic inflammation drive synaptic dysfunction and cognitive decline. Molecular hydrogen (H2) has emerged as a candidate neuroprotective gas with selective antioxidant and anti-inflammatory properties, although its efficacy in amyloid-driven pathology remains incompletely defined. In this study, 5xFAD transgenic mice harboring human amyloid precursor protein (APP) and presenilin-1 (PSEN1) mutations and age-matched C57BL/6 wild-type mice were exposed to 2% H2 by inhalation for 1 h/day over 4 weeks. H2 inhalation reduced hippocampal reactive oxygen species (ROS), increased systemic catalase activity, and enhanced hippocampal ATP levels. In serum, H2 decreased tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β, restored IL-10, and partially normalized IL-13, shifting the peripheral environment toward a less pro-inflammatory profile. In the hippocampus, H2 upregulated nuclear factor erythroid 2-related factor 2 (NRF2), attenuated nuclear factor kappa B (NF-κB) activation, reduced the BAX/BCL-2 ratio, preserved neuronal nuclei (NEUN) expression, and decreased hippocampal Aβ42 burden. Collectively, these findings indicate that H2 inhalation confers multi-faceted neuroprotection in 5xFAD mice by restoring redox homeostasis, suppressing inflammation, improving mitochondrial function, and limiting Aβ accumulation.