Abstract

Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxiety and cognitive function. The molecular mechanisms by which RSV restores or improves behavioral abnormalities in animal models encompass both normalization of central and peripheral immune alteration and oxidative stress markers and new molecular mechanisms such as expression of cortical gamma-amino butyric acid neurons, certain type of miRNAs that regulate spine growth. One randomized, placebo-controlled clinical trial (RCT) suggested that RSV add-on risperidone therapy improves comorbid hyperactivity/non-compliance, whereas no effects where seen in core symptoms of ASD No RCTs about the effect of RSV as monotherapy have been performed and the results from preclinical studies encourage its feasibility. Further clinical trials should also identify those ASD patients with immune alterations and/or with increased oxidative stress markers that would likely benefit from RSV administration.

Highlights

  • Autism spectrum disorder (ASD) has been defined as a set of developmental disabilities characterized by social impairments, communication difficulties and restricted and stereotyped patterns of behavior [1]

  • There are numerous lines of evidence suggesting that Propionic acid (PPA) and other enteric short-chain fatty acids may be elevated in ASD

  • Studies using this model have found that ICV treatment of PPA is capable of inducing numerous behavioral, electrophysiological and neuropathological changes in rats that are consistent with those observed in ASD

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Summary

Introduction

Autism spectrum disorder (ASD) has been defined as a set of developmental disabilities characterized by social impairments, communication difficulties and restricted and stereotyped patterns of behavior [1]. Different research claims that there are a multitude of alterations associated with autism, but 25% of all cases of autism are related to these genes [4]. There are several causes that have been associated to the pathophysiology of ASD (Figure 1), among them the strongest evidence has been proven for immune dysregulation/inflammation and oxidative stress, followed by toxicant exposures and mitochondrial dysfunction measured in circulating blood leukocytes [5]. James et al [6] found differences in the antioxidant capacity and in the concentration of several metabolites related with oxidative stress in 80 subjects with autism compared with healthy children

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