ABSTRACT
Aims
Oxidative stress has recently emerged as a key factor in the pathophysiology of schizophrenia. This study investigated whether inhalation therapy with hydrogen gas, a selective antioxidant, could reduce oxidative stress and improve behavioral outcomes in an MK-801–induced schizophrenia-like mouse model.
Methods
Six-week-old male C57BL/6 mice received chronic intraperitoneal injections of MK-801 (0.5 mg/kg) or saline for 4 weeks. A third group received MK-801 followed by hydrogen gas inhalation therapy. Behavioral assessments included the open-field test (OFT) to evaluate hyperactivity as an indicator of positive symptoms and the prepulse inhibition (PPI) test to assess cognitive dysfunction. Oxidative stress was evaluated by measuring whole-brain hydroxyl radical antioxidant capacity (HORAC) and total antioxidant capacity (TAC).
Results
MK-801–treated mice exhibited significant hyperactivity in the OFT and a trend toward impaired PPI, confirming the schizophrenia-like phenotype. Hydrogen gas treatment did not produce significant improvements. MK-801 administration significantly reduced HORAC levels, whereas hydrogen gas therapy markedly restored them. No significant differences in TAC were observed among the groups.
Conclusion
These findings suggest that hydrogen gas therapy does not significantly ameliorate behavioral abnormalities in the MK-801–induced schizophrenia-like mouse model but exerts beneficial antioxidant effects. Future studies should evaluate hydrogen gas as an adjunctive therapy and further assess its efficacy and safety in clinical settings.