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

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. T...

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Main Authors: Qingjun Guo, Xi Yin, Meng Qiao, Yujiao Jia, Dandan Chen, Juan Shao, Tyler W. Lebaron, Yuan Gao, Haishui Shi, Bin Jia
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-08-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnbeh.2018.00170/full
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author Qingjun Guo
Xi Yin
Meng Qiao
Yujiao Jia
Dandan Chen
Juan Shao
Tyler W. Lebaron
Yuan Gao
Yuan Gao
Haishui Shi
Haishui Shi
Haishui Shi
Haishui Shi
Bin Jia
Bin Jia
author_facet Qingjun Guo
Xi Yin
Meng Qiao
Yujiao Jia
Dandan Chen
Juan Shao
Tyler W. Lebaron
Yuan Gao
Yuan Gao
Haishui Shi
Haishui Shi
Haishui Shi
Haishui Shi
Bin Jia
Bin Jia
author_sort Qingjun Guo
collection DOAJ
description 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.
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spelling doaj.art-12be88c564614848b9418954d163d4972022-12-22T02:20:16ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532018-08-011210.3389/fnbeh.2018.00170365854Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice OffspringQingjun Guo0Xi Yin1Meng Qiao2Yujiao Jia3Dandan Chen4Juan Shao5Tyler W. Lebaron6Yuan Gao7Yuan Gao8Haishui Shi9Haishui Shi10Haishui Shi11Haishui Shi12Bin Jia13Bin Jia14Department of Surgery, Hebei Medical University, Shijiazhuang, ChinaDepartment of Functional Region of Diagnosis, Hebei Medical University Fourth Hospital, Hebei Medical University, Shijiazhuang, ChinaCollege of Basic Medicine, Hebei Medical University, Shijiazhuang, ChinaCollege of Basic Medicine, Hebei Medical University, Shijiazhuang, ChinaCollege of Basic Medicine, Hebei Medical University, Shijiazhuang, ChinaDepartment of Senile Disease, The Third Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, ChinaMolecular Hydrogen Foundation, Kissimmee, FL, United StatesDepartment of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, ChinaNeuroscience Research Center, Hebei Medical University, Shijiazhuang, ChinaDepartment of Biochemistry and Molecular Biology, Hebei Medical University, Shijiazhuang, ChinaNeuroscience Research Center, Hebei Medical University, Shijiazhuang, ChinaHebei Key Laboratory of Forensic Medicine, Department of Forensic Medicine, Shijiazhuang, ChinaCollaborative Innovation Center of Forensic Medical Molecular Identification, Hebei Medicial University, Shijiazhuang, ChinaNeuroscience Research Center, Hebei Medical University, Shijiazhuang, China0Lingshui General Hospital, Lingshui, ChinaDue 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.https://www.frontiersin.org/article/10.3389/fnbeh.2018.00170/fullmolecular hydrogenautismvalproic acidinflammationinterleukin 6tumor necrosis factor-α
spellingShingle Qingjun Guo
Xi Yin
Meng Qiao
Yujiao Jia
Dandan Chen
Juan Shao
Tyler W. Lebaron
Yuan Gao
Yuan Gao
Haishui Shi
Haishui Shi
Haishui Shi
Haishui Shi
Bin Jia
Bin Jia
Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring
Frontiers in Behavioral Neuroscience
molecular hydrogen
autism
valproic acid
inflammation
interleukin 6
tumor necrosis factor-α
title Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring
title_full Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring
title_fullStr Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring
title_full_unstemmed Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring
title_short Hydrogen-Rich Water Ameliorates Autistic-Like Behavioral Abnormalities in Valproic Acid-Treated Adolescent Mice Offspring
title_sort hydrogen rich water ameliorates autistic like behavioral abnormalities in valproic acid treated adolescent mice offspring
topic molecular hydrogen
autism
valproic acid
inflammation
interleukin 6
tumor necrosis factor-α
url https://www.frontiersin.org/article/10.3389/fnbeh.2018.00170/full
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