Beneficial effects of xenon inhalation on behavioral changes in a valproic acid-induced model of autism in rats

A P Dobrovolsky,A V Malyshev,V R Gedzun,D Ma,V A Dubynin,V I Bogin,Iu A Sukhanova,T E Ichim

doi:10.1186/s12967-019-02161-6

A P Dobrovolsky, A V Malyshev + Show 6 more

Open Access

https://doi.org/10.1186/s12967-019-02161-6

Copy DOI

Abstract

BackgroundXenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery. Its antagonistic effect on glutamate subtype of NMDA (N-methyl-d-aspartate) receptors resulted in evaluation of this gas for treatment of CNS pathologies, including psychoemotional disorders. The aim of this study was to assess the behavioral effects of acute inhalation of subanesthetic concentrations of Xe and to study the outcomes of Xe exposure in valproic acid (VPA)-induced rodent model of autism.MethodsWe have conducted two series of experiments with a battery of behavioral tests aimed to evaluate locomotion, anxiety- and depression-like behavior, and social behavior in healthy, VPA-treated and Xe-exposed young rats.ResultsWe have shown that in healthy animals Xe exposure resulted in acute and delayed decrease of exploratory motivation, partial decrease in risk-taking and depressive-like behavior as well as improved sensorimotor integration during the negative geotaxis test. Acute inhalations of Xe in VPA-exposed animals led to improvement in social behavior, decrease in exploratory motivation, and normalization of behavior in forced-swim test.ConclusionBehavioral modulatory effects of Xe are probably related to its generalized action on excitatory/inhibitory balance within the CNS. Our data suggest that subanesthetic short-term exposures to Xe have beneficial effect on several behavioral modalities and deserves further investigation.

Highlights

Xenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery
There was a tendency towards the decrease in time spent in the center of the arena (p = 0.052) in “Xe” group vs. “Control” group
Elevated‐plus maze Xe-exposed and air-exposed rats showed no differences in time spent in the open arms, time spent in the closed arms, time spent in the center, number of open and closed arm entries, rears and grooms (p > 0.45; data not shown)

Summary

Introduction

Xenon (Xe) is a noble gas that has been used for the last several decades as an anesthetic during surgery. Its antagonistic effect on glutamate subtype of NMDA (N-methyl-d-aspartate) receptors resulted in evaluation of this gas for treatment of CNS pathologies, including psychoemotional disorders. Etiology of ASD appears to be rather heterogeneous and includes both genetic predisposition and environmental exposure at the early stages of development [4]. There are a number of probable mechanisms underlying the development of ASD, including alterations in glutamatergic/GABAergic neurotransmission, inflammatory signals, and oxidative stress-related systems, which may explain neurobiological susceptibilities to adverse environmental exposures [5]. Such heterogeneity suggests that no single treatment or diagnostic biomarker is likely to be found for autism [3]

Objectives

Methods

Results

Discussion

Conclusion