Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by impairments in social communication, repetitive behaviors, restricted interests, and hyperesthesia/hypesthesia caused by genetic and/or environmental factors. In recent years, inflammation and oxidative stress have been implicated in the pathogenesis of ASD. In this review, we discuss the inflammation and oxidative stress in the pathophysiology of ASD, particularly focusing on maternal immune activation (MIA). MIA is a one of the common environmental risk factors for the onset of ASD during pregnancy. It induces an immune reaction in the pregnant mother’s body, resulting in further inflammation and oxidative stress in the placenta and fetal brain. These negative factors cause neurodevelopmental impairments in the developing fetal brain and subsequently cause behavioral symptoms in the offspring. In addition, we also discuss the effects of anti-inflammatory drugs and antioxidants in basic studies on animals and clinical studies of ASD. Our review provides the latest findings and new insights into the involvements of inflammation and oxidative stress in the pathogenesis of ASD.

Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

“…As mentioned above, immune dysregulation, inflammation, oxidative stress, and mitochondrial dysfunction are closely associated with ASD and are important physiological and metabolic abnormalities in ASD 128,138,168–170 . They may be the intersection of genetic and environmental factors and contribute to ASD.…”

“…A mechanistic modeling based on transcriptome suggested a direct link between inflammation and ASD in neurons 118 . Notedly, the MIA is a one of the common environmental risk factors of ASD pathology during pregnancy 126–128 . The adaptive immune pathway was enriched in maternal blood from mothers of children later diagnosed with ASD by transcriptome 129 .…”

The role and impact of abnormal vitamin levels in autism spectrum disorders

“…121 Recent studies have shown that low serum vitamin B12 levels are associated with increased levels of oxidative stress and poor DNA methylation in children with ASD and that VB12 is crucial for processes dependent on DNA methylation in the brain. 122 DNA methylation is an important epigenetic regulatory system during early brain development, and differences in DNA methylation were also found in four separate areas in the temporal cortex and cerebellum with varied levels of methylation when postmortem brain tissue from ASD patients was examined. 123…”

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

“…Several meta-analyses have confirmed a strong involvement of neuroinflammatory processes in practically all neuropsychiatric and/or neurodegenerative diseases including ASD [2,[35][36][37][38][39][40][41][42][43][44]. Thus, it has been reported that individuals with ASD have significantly higher levels of several inflammatory biomarkers, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and C-reactive protein (CRP) compared to healthy controls [37].…”

“…As mentioned earlier, no cure for ASD is yet available. However, research in this area and potential use of anti-inflammatory drugs and antioxidants as well as mesenchymal stem cell-based therapy have been suggested [40,44]. Recently, involvement of the histaminergic system and potential therapeutic exploitation of this system in ASD and other conditions associated with impairment in executive functioning was provided [39].…”