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

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

“…As previously reported [11], many of the autism genes in this set are involved in barrier functions across several different boundaries (blood/brain, skin, intestinal and placental) and also in the control of respiratory cilia that clear the airways of noxious particles. Evidently, environmental chemicals have to traverse such boundaries.…”

“…Bile acids act as nutrient signalling hormones and activate a number of nuclear receptors and G-protein coupled receptors including a specific bile acid receptor GPBAR1 which regulates intestinal barrier structure via modification of epithelial tight junctions [204]. Many of the ASG's are implicated in barrier function and intestinal permeability increases (leaky gut) have been reported in autism [11,205]. No studies relating bile acids to autism were found in Pubmed, but this area appears to be of interest.…”

“…No relationships with autism or neurodevelopment have been reported. Given the barrier and ciliary function of many autism genes [11], it is perhaps this aspect rather than neurodevelopmental criteria that provides such a high score.…”

“…In addition the offspring show impaired motor coordination and motor learning ability coupled with a reduction in the cerebellar size and impairment in the cerebellar foliation profile [263,264]. A 3 day exposure to 2.5 mg/kg tretinoin (gestational days [11][12][13] produces a 10% reduction in weight of cerebellum at 4 weeks of age, not accompanied by other malformations [265]. In rats treated with retinoic acid at gestational day E10, the foetuses show structural changes similar to humans with Arnold-Chiari malformation, including downward displacement of the cerebellum to just above the foramen magnum and compression of the developing medulla into a small posterior fossa [266].…”

“…These barrier-related genes are thus in a position to modify the access of numerous environmental agents to the blood and brain and their role in respiratory cilia is relevant to particulate matter and airborne pollutants [11].…”