Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders

Abstract

The prevalence of autism spectrum disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes, and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity and calcium regulation. The previous review already described extrinsic factors, including deficient dietary supplementation, and exposure to oxidative stress, infections and inflammation that can disrupt signaling of the PGE2 pathway and contribute to ASDs. In this review, the structure and establishment of two key protective barriers for the brain during early development are described: the blood-brain barrier; and the placental barrier. Then, the first comprehensive summary of other environmental factors, such as exposure to chemicals in air pollution, pesticides and consumer products, which can also disturb PGE2 signaling and increase the risk for developing ASDs is provided. Also, how these exogenous agents are capable of crossing the protective barriers of the brain during critical developmental periods when barrier components are still being formed is described. This review underlines the importance of avoiding or limiting exposure to these factors during vulnerable periods in development.

Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses

“…Exposure to PCB and PBDE seems to alter calcium-related signaling pathway, leading to alterations in dendritic growth and subsequent abnormalities in neuronal connectivity, a key feature of ASD [106, 107]. Prostaglandin E2 (PGE2) is an important regulatory element in calcium homeostasis and synaptic plasticity in the developing brain [108, 109]. Evidence suggests disruption of PGE2 as a possible mechanism for the effect of organic chemicals, inflammation, and infection on risk of ASD [109].…”

“…Prostaglandin E2 (PGE2) is an important regulatory element in calcium homeostasis and synaptic plasticity in the developing brain [108, 109]. Evidence suggests disruption of PGE2 as a possible mechanism for the effect of organic chemicals, inflammation, and infection on risk of ASD [109]. …”

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…These are grouped by general function in Fig 9. They include compounds related to oxidative stress and folate/methionine/homocysteine metabolism which play key roles in autism [192][193][194][195] as do cholesterol and fatty acid metabolism [196][197][198][199] or inflammation [200][201][202][203]..…”

The barrier, airway particle clearance, placental and detoxification functions of autism susceptibility genes

“…The importance of barrier function in relation to multiple environmental pollutants and autism, particularly during critical developmental periods when barrier components are still being formed has also been noted by others (Julio-Pieper et al, 2014;Liu et al, 2005;Ratajczak, 2011;Viggiano et al, 2015;Wong et al, 2015).…”

“…Their distribution is relevant to the many pollutants implicated in autism (Grandjean and Landrigan, 2014;Rossignol et al, 2014), which have to cross such barriers, and to the "leaky gut" scenario in autism (de Magistris et al, 2010;Liu et al, 2005;White, 2003). The importance of the blood brain barrier in autism has been stressed by others (Demeestere et al, 2015;Wong et al, 2015), although its integrity, or that of the skin or airway barriers, do not appear to have been assessed in human studies. Many autism genes are also expressed and enriched in organs of detoxification (liver and kidney) and in endocrine organs releasing steroid hormones relevant to neurodevelopment and to studies relating environmental endocrine disruptors to autism (de Cock et al, 2012;Kajta and Wojtowicz, 2010;Kajta and Wojtowicz, 2013;Kalkbrenner et al, 2014).…”