Molecular hydrogen inhibits neuroinflammation and ameliorates depressive-like behaviors and short-term cognitive impairment in senescence-accelerated mouse prone 8 mice.

BACKGROUND AND AIMS: Neuroinflammation, a low-grade chronic inflammation of the central nervous system, is linked to age-related neuropsychiatric disorders such as senile depression and Alzheimer's disease. Recent studies have explored controlling neuroinflammation as a novel treatment strategy. Molecular hydrogen shows anti-inflammatory effects. However, its impacts on neuroinflammation and age-related neuropsychiatric disorders remain unelucidated. We investigated molecular hydrogen's effects on microglial activation, neuroinflammation, depressive-like behavior, and short-term cognitive decline in senescence-accelerated mouse-prone 8 (SAMP8) mice.

METHODS

Six-week-old SAMP8 or senescence-accelerated mouse-resistant 1 (SAMR1) mice received hydrogen-rich jelly (HRJ) or placebo jelly (PJ) from six weeks of age for 26-28 weeks. Depressive-like behavior was assessed using tail suspension and forced swimming tests, while cognitive function was evaluated using the Y-maze and object recognition tests. Brain tissues were used for immunohistochemical studies or to measure pro-inflammatory cytokine levels via enzyme-linked immunosorbent assay (ELISA).

RESULTS

HRJ intake reduced immobility time in both tail suspension and forced swimming tests and enhanced visual cognitive and spatial working memory in SAMP8 mice. Additionally, HRJ intake suppressed the 8-hydroxy-2'-deoxyguanosine (8-OHdG), Iba1, and cleaved caspase 3 expression levels in the medial prefrontal cortex and hippocampal dentate gyrus. Furthermore, HRJ intake significantly lowered IL-6 levels in brain tissues of SAMP8 mice.

CONCLUSIONS

These findings suggest that molecular hydrogen treatment may regulate neuroinflammation induced by activated microglia and improve depressive-like behavior and short-term cognitive impairment in SAMP8 mice.