Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring.

Abstract

Using a valproic acid (VPA) mouse model of autism, this study examined whether hydrogen-rich water (HRW) could reduce neurodevelopmental behavioral deficits in adolescent offspring. Pregnant ICR mice received intraperitoneal VPA (600 mg/kg) on gestational day 12.5, and offspring were given HRW across different postnatal windows (PND 1–21, PND 13–21, or PND 13–42). Behavioral assessments conducted between PND 35–42 — including open field, social interaction, novelty-suppressed feeding, hot plate, and contextual fear memory tests — showed that HRW significantly reversed the autistic-like deficits in both male and female offspring. Serum levels of IL-6 and TNF-α, which were elevated by maternal VPA exposure, were normalized by HRW administration, whereas BDNF levels remained unaffected. These findings indicate that anti-inflammatory mechanisms may underlie HRW's ameliorating effects on autism-related behavioral phenotypes, warranting further investigation into its preventive potential for neurodevelopmental conditions.

Mechanism

HRW is proposed to reduce VPA-induced neuroinflammation by normalizing elevated serum IL-6 and TNF-α levels, thereby alleviating autism-like behavioral abnormalities without affecting BDNF concentrations.