Hydrogen Gas Helps Brain Function in Sepsis Mice by Protecting Memory
- Authors
- Mingdong Yu, Chao Qin, Pei Li, Yingli Zhang, Ying Wang, Jing Zhang, Dedong Li, Huixing Wang, Yuechun Lu, Keliang Xie, Yang Yu, Yonghao Yu
- Journal
- International Immunopharmacology
- Year
- 2021
- DOI
- 10.1016/j.intimp.2021.107583
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- China
- Health Condition
- Sepsis
- Body System
- Nervous System
TL;DR
Inhaling 2% hydrogen gas helps improve brain function and reduce inflammation in mice with sepsis-related brain damage by affecting how certain genes are controlled.
Key Finding
Inhaling 2% hydrogen gas reduced brain inflammation and improved cognitive function in septic mice by decreasing the methylation (chemical marking) of a gene region that controls BDNF, a protein essential for brain health and memory.
Summary
In mice with sepsis-induced brain inflammation, researchers tested whether inhaling 2% hydrogen gas could improve cognitive function and reduce brain damage. They found that hydrogen gas reduced inflammatory molecules in the brain, altered how certain genes were chemically marked (a process called methylation), increased levels of a protein important for brain health called BDNF, and improved the mice's memory and learning abilities in tests.
Practical Takeaway
This mouse study suggests hydrogen gas inhalation may help protect brain function during severe infection by working through an epigenetic mechanism (changes in how genes are chemically marked). However, this is early-stage research in animals only—human studies would be needed to determine if these effects apply to sepsis patients, and the study does not provide information about safety or optimal dosing for humans.
Abstract
Sepsis-associated encephalopathy (SAE) can cause acute and long-term cognitive impairment and increase the mortality rate in sepsis patients, and we previously reported that 2% hydrogen gas (H2) inhalation has a therapeutic effect on SAE, but the underlying mechanism remains unclear. Dynamic DNA methylation, which catalyzed by DNA methyltransferases (DNMTs), is involved in the formation of synaptic plasticity and cognitive memory in the central nervous system. And brain-derived neurotrophic factor (BDNF), to be a key signaling component in activity-dependent synaptic plasticity, can be induced by neuronal activity accompanied by hypomethylation of its promoter IV. This study was designed to illustrate whether H2 can mediate SAE by alter the BDNF promoter IV methylation mediated by DNMTs. We established an SAE model by cecal ligation and perforation (CLP) in C57BL/6 mice. The Morris water maze test from the 4th to the 10th day after sham or CLP operations were used to evaluate mouse cognitive function. Hippocampal tissues were isolated at the 24 after sham or CLP surgery. Pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and High Mobility Group Box 1 (HMGB1) were measured by enzyme-linked immunosorbent assay (ELISA). mRNA or protein levels of DNMTs (DNMT1, DNMT3a and DNMT3b), BDNF promoter IV and total BDNF were detected by RT-PCR and Western blot tests. Immunofluorescence staining were used to determine the expressions of DNMT1 and DNMT3a. The quantitative methylation analysis of the 11 CpG island of the promoter region of BDNF exon IV was determined using theAgena's MassARRAY EpiTYPER system. We found that 2% H2 inhalation can reduce pro-inflammatory factors, alleviate DNMT1, DNMT3a but not DNMT3b expression, make hypomethylation of BDNF promoter IV at 5 CpG sites, enhance the BDNF levels and then decrease escape latency but increase platform crossing times in septic mice. Our results suggest that 2% H2 inhalation may alleviate SAE through altering the regulation of BDNF promoter IV methylation which mediated by DNMT1 and DNMT3a in the hippocampus of septic mice.