Exposure to Neurotoxins In Utero Links Atopic Dermatitis to Autism Spectrum Disorder

Exposure to neurotoxins in utero revealed selective cytotoxicity in both the brain and epidermis and explains a baseline association of atopic dermatitis (AD) with a subset of autism spectrum disorder (ASD).

Researchers explored the mechanistic basis for the AD-ASD association in a valproic acid (VPA) murine model. They hypothesized that cutaneous involvement could be detected in experiments conducted in VPA-treated BALB/c mice. Mid-trimester pregnant mice were given a single intraperitoneal injection of either valproic acid sodium salt dissolved in saline or saline along on embryonic day 12.5 and were housed individually until postnatal day 21. Brain, skin, and blood samples were taken at various postnatal time points for histology and quantitation of tissue sphingolipid content and cytokine levels.

By day 1 postpartum in both the VPA-treated mouse skin and brain, AD-like changes in ceramide content occurred. Elevated cytokine markers of toxicity and/or chronic inflammation (ie, TNF-α, IL-17A and IFNγ) at birth were observed and indicate structural evidence of cytotoxicity in both the brain and epidermis.

“Baseline involvement of both AD and ASD could reflect concurrent neuro- and epidermal toxicity, possibly because both epidermis and neural tissues originate from the embryonic neuroectoderm,” concluded the study authors. “These studies illuminate the shared susceptibility of the brain and epidermis to a known neurotoxin, suggesting that the atopic diathesis could be extended to include ASD,” they continued.

Reference
Shin KO, Crumrine DA, Kim S, et al. Phenotypic overlap between atopic dermatitis and autism. BMC Neurosci. 2021;22(1):43. doi:10.1186/s12868-021-00645-0