Phenotypic overlap between atopic dermatitis and autism

BMC Neuroscience

Katrina Abuabara¹  Kyong-Oh Shin²  Sungeun Kim²  Bogyeong Kim²  Kyungho Park²  Yerin Lee²  Sekyoo Jeong³  Yoshikazu Uchida⁴  Chaehyeong Park⁴  Jason M. Meyer⁴  Joan S. Wakefield⁴  Peter M. Elias⁴  Debra A. Crumrine⁴  Byeong Deog Park⁵ 

[1] Department of Dermatology, University of San Francisco, San Francisco, CA, USA;Department of Food Science/Nutrition, & Convergence Program of Material Science for Medicine/Pharmaceutics, and the Korean Institute of Nutrition, Hallym University, Chuncheon, South Korea;Dept of Cosmetic Science, Seowon University, Cheongju, South Korea;Dept. of Dermatology, University of California, NCIRE, and Veterans Affairs Medical Center, 4150 Clement Street, MS 190, 94121, San Francisco, CA, USA;Sphingobrain Inc., San Francisco, CA, USA;Dr. Raymond Laboratories, Inc, Englewood Cliffs, NJ, USA;

关键词: Atopic dermatitis;    Autism;    Autism spectrum disorders;    Blood–brain barrier;    IFNγ;    IL-4, 5, 13 and 17A;    TNFα;    Valproic acid mouse model;   

DOI  :  10.1186/s12868-021-00645-0

来源: Springer

【 摘 要 】

BackgroundAutism, a childhood behavioral disorder, belongs to a large suite of diseases, collectively referred to as autism spectrum disorders (ASD). Though multifactorial in etiology, approximately 10% of ASD are associated with atopic dermatitis (AD). Moreover, ASD prevalence increases further as AD severity worsens, though these disorders share no common causative mutations. We assessed here the link between these two disorders in the standard, valproic acid mouse model of ASD. In prior studies, there was no evidence of skin involvement, but we hypothesized that cutaneous involvement could be detected in experiments conducted in BALB/c mice. BALB/c is an albino, laboratory-bred strain of the house mouse and is among the most widely used inbred strains used in animal experimentation.MethodsWe performed our studies in valproic acid (VPA)-treated BALB/c hairless mice, a standard mouse model of ASD. Mid-trimester pregnant mice received a single intraperitoneal injection of either valproic acid sodium salt dissolved in saline or saline alone on embryonic day 12.5 and were housed individually until postnatal day 21. Only the brain and epidermis appeared to be affected, while other tissues remain unchanged. At various postnatal time points, brain, skin and blood samples were obtained for histology and for quantitation of tissue sphingolipid content and cytokine levels.ResultsAD-like changes in ceramide content occurred by day one postpartum in both VPA-treated mouse skin and brain. The temporal co-emergence of AD and ASD, and the AD phenotype-dependent increase in ASD prevalence correlated with early appearance of cytokine markers (i.e., interleukin [IL]-4, 5, and 13), as well as mast cells in skin and brain. The high levels of interferon (IFN)γ not only in skin, but also in brain likely account for a significant decline in esterified very-long-chain N-acyl fatty acids in brain ceramides, again mimicking known IFNγ-induced changes in AD.ConclusionBaseline 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. 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.

【 授权许可】

CC BY