Phenotypic overlap between atopic dermatitis and autism

Abstract

Background: Autism, 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.Methods: We performed our studies in valproic acid (VPA)-treated BALB/c hairless mice. 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 post-natal time points, brain, skin and blood samples were obtained for histology and for quantitation of tissue sphingolipid content and cytokine levels.Results: AD-like changes in ceramide content occurred by day one post-partum 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 the early appearance of Th2 markers (i.e., interleukin [IL]-4, 5, & 13, mast cells) in the skin and brain. The high levels of interferon (IFN)g not only in skin, but also in brain likely account for a significant decrease in very-long-chain N-acyl fatty acids in brain ceramides that again mimicked known IFNg-induced changes in AD. Conclusion: The baseline involvement of both AD and ASD could reflect concurrent neuro- and epidermal toxicity, possibly because both the 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 ASD could be included within the atopic diathesis.

The potential of using exosomes in modern medicine

“…Dostrzeżono, że wyżej wymienione, korzystne efekty były zależne od dawki egzosomów. Co więcej, ASC-exos stymulował produkcję ceramidów i dihydroceramidów, które są istotne dla odbudowy bariery skórnej [23]. Na podstawie tych badań można wnioskować, że systemowe podawanie ASCexos może stanowić obiecującą bezkomórkową terapię w leczeniu AZS poprzez regulację odpowiedzi zapalnych i przywrócenie funkcji bariery naskórkowej.…”

Research advances in prevention and treatment of burn wound deepening in early stage

“…For example, mesenchymal stem cell-derived exosomes (MSC-exosomes) are enriched with various miRNAs and proteins that mediate multiple intercellular signaling pathways and reduce inflammation by regulating the levels of various cytokines, including transforming growth factor-β1 (TGF-β1), hepatocyte growth factor (HGF), nitric oxide (NO), and interleukin-4 (IL-4) (17). MSCs can induce regeneration of the epidermal skin barrier by increasing the synthesis of ceramide and dihydroceramides (18). In addition to these functions, MSCs can also support angiogenesis through paracrine influences.…”