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

Qingjun Guo,Haishui Shi,Tyler W Lebaron,Meng Qiao,Bin Jia,Xi Yin,Juan Shao,Yuan Gao,Yujiao Jia,Dandan Chen

doi:10.3389/fnbeh.2018.00170

Abstract

Due to its anti-inflammatory and anti-oxidative effects, recent research has demonstrated that molecular hydrogen can serve as a new medical approach for depression, anxiety and traumatic brain injury. However, its potential effects on neurodevelopmental diseases, such as autism are still elusive. The present study aims to investigate the potential effects of hydrogen-rich water (HRW) administration on valproic acid (VPA)-induced autistic-like behavioral deficits, and the associated underlying mechanism in adolescent mice offspring. Pregnant ICR mice were randomly divided into five groups (n = 6). One group was injected with saline (NAV group) and provided hydrogen-free water. The other four groups were injected with VPA (600 mg/kg, intraperitoneally, i.p.) on pregnant day (PND) 12.5. One group was provided with hydrogen-free water (VEH group) and the other three groups were provided HRW at different segments, postnatal day 1 (PND 1) to PND 21 (PHV group), PND 13 to PND 21 (PVS group) or from PND 13 to postnatal day 42 (PVL group). Behavioral tests, including open field, novelty suppressed feeding (NSF), hot plate, social interaction (SI) and contextual fear memory tests were conducted between postnatal day 35–42. We found that HRW administration significantly reversed the autistic-like behaviors induced by maternal VPA exposure in the adolescent offspring of both male and female adolescent offspring. Furthermore, HRW administration significantly reversed the alternation of serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), but without any effects on the BDNF levels in maternal VPA-exposed mice offspring. These data suggest the need for additional research on HRW as a potential preventive strategy for autism and related disorders.Lay Summary: Maternal VPA injection induces autistic-like behavioral deficits in adolescent mice offspring. HRW administration ameliorates autistic-like behavioral deficits. HRW administration reverses the alternation of serum levels of IL-6 and TNF-α induced by VPA.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with persistent impairments of social interactions (SIs), communication deficits, restricted repetitive behavior and higher anxiety-like behaviors (Hollocks et al, 2014; Chahrour et al, 2016)
Based on the dysregulation of the immune system of autism, and the anti-inflammatory characteristics of hydrogen, the present study aimed to investigate the potential effects of hydrogen-rich water (HRW) on autistic-like behaviors using a maternal valproic acid (VPA)exposed-mice model, and explore the associated mechanism focusing on the peripheral serum levels of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) assessed by EnzymeLinked Immune-Sorbent Assay (ELISA) analysis
Post hoc analysis showed that HRW administration in the PHV (P < 0.001 for male and P < 0.05 for female respectively), PVS (P < 0.001 for male and P < 0.001 for female) and PVL (P < 0.001 for male) significantly decreased the latency to feeding compared with that of VPA-exposed mice offspring

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with persistent impairments of social interactions (SIs), communication deficits, restricted repetitive behavior and higher anxiety-like behaviors (Hollocks et al, 2014; Chahrour et al, 2016). Increasing scientific data links both peripheral and brain inflammation with the pathogenic development of autism. Those with autism exhibit signs of neuroinflammation, dysregulated inflammatory responses and immune abnormalities. These characteristics are observed in the perinatal period, and throughout life (Masi et al, 2017; Meltzer and Van de Water, 2017; Prata et al, 2017; Varghese et al, 2017). Results from postmortem studies showed that patients with ASD have neuroinflammation in certain areas of the brain, and further analyses suggest a strong immune response (Lee et al, 2017; Varghese et al, 2017; Courchesne et al, 2018). Anti-inflammatory strategies and antioxidants exert significant anti-autistic-like effects in animals and in individuals with autism (Bronson and Bale, 2014; Singh et al, 2014; Al-Amin et al, 2015)

Methods

Results

Conclusion