Oxidative Stress and Immune System Dysfunction in Autism Spectrum Disorders

Abstract

Autism Spectrum Disorders (ASDs) represent a group of neurodevelopmental disorders associated with social and behavioral impairments. Although dysfunctions in several signaling pathways have been associated with ASDs, very few molecules have been identified as potentially effective drug targets in the clinic. Classically, research in the ASD field has focused on the characterization of pathways involved in neural development and synaptic plasticity, which support the pathogenesis of this group of diseases. More recently, immune system dysfunctions have been observed in ASD. In addition, high levels of reactive oxygen species (ROS), which cause oxidative stress, are present in ASD patients. In this review, we will describe the major alterations in the expression of genes coding for enzymes involved in the ROS scavenging system, in both ASD patients and ASD mouse models. In addition, we will discuss, in the context of the most recent literature, the possibility that oxidative stress, inflammation and immune system dysfunction may be connected to, and altogether support, the pathogenesis and/or severity of ASD. Finally, we will discuss the possibility of novel treatments aimed at counteracting the interplay between ROS and inflammation in people with ASD.

Exenatide, a GLP‐1 analog, has healing effects on LPS‐induced autism model: Inflammation, oxidative stress, gliosis, cerebral GABA, and serotonin interactions

“…It was reported in the 1970s that ASD was more frequent in children exposed to infection during the intrauterine period or those who received vaccines such as mumps, measles, and rubella (Mori, Murata, & Handa, 1975). Increased inflammation and oxidative stress have also been shown to have an important place in the etiology of ASD in further studies (Pangrazzi, Balasco, & Bozzi, 2020). For example, in a meta‐analysis conducted by Saghazadeh et al (2019), tumor necrosis factor‐alpha (TNF‐α), interferon‐gamma (IFN‐γ), interleukin‐1 beta (IL‐1β), and IL‐6 levels were higher in the peripheral blood of patients with autism compared to healthy individuals.…”

The Parvalbumin Hypothesis of Autism Spectrum Disorder

“…Importantly, in the absence of PV, ROS production is significantly higher in mice older than 1 month and the relative increase is approximately proportional to the PV concentration in WT Pvalb neurons . An elevation in ROS levels causing an imbalance in redox homeostasis has been suggested as a pathophysiological mechanism of ASD (Tang et al, 2013;Pangrazzi et al, 2020). Increased ROS levels have also been observed in postmortem brain tissue of children with ASD (Siddiqui et al, 2016).…”

The Gut Microbiota and Oxidative Stress in Autism Spectrum Disorders (ASD)

“…Additionally, glutathione can also obliterate toxic substances from the cells in its role as a cofactor for GSH transferase [ 46 , 48 ]. In general, the brain is very sensitive to the accumulation of radicals such as ROS on account of the relatively weak protective mechanisms [ 49 , 50 ].…”