Allergic dermatitis (AD), associated with pruritus and itchiness, is one of the major stressful conditions early in life. AD also influences the incidence of neuropsychiatric disorders and developmental disorders through neuro-immune interactions. To the best of our knowledge, there is no report that assesses the effects of early childhood dermatitis on psychiatric disorders later in life using an animal model. Here, we developed an oxazolone (Ox)-induced AD model in the early life of male C57BL/6J mice whose ears were challenged by Ox repeatedly from postnatal days (PD) 2 to PD30. On PD30, the Ox-treated ears were remarkably thickened and showed epidermal hyperplasia coupled with increased expression of T helper 2 cytokines, interleukin (IL)-4, and IL-13 in the ear tissue. Additionally, serum immunoglobulin E levels and serum corticosterone levels were higher in the Ox-treated mice than those in the control mice. Although Ox-treated PD40 mice showed neither behavioral abnormalities nor increases in pro-inflammatory cytokine expression in the brain, this study revealed that they experienced downregulation of CD200R1 expression in the amygdala under basal conditions and that additional lipopolysaccharide (LPS) administration induced enhanced neuroinflammatory reaction as the priming effect was accompanied by an increase of Iba-1-positive microglia in the amygdala and hippocampus. Furthermore, the Ox-treated PD40 mice showed depressive-like behaviors 24 h after LPS administration, whereas the control mice did not. Interestingly, the expression of indoleamine 2,3-dioxygenase and kynurenine 3-monooxygenase, key rate-limiting enzymes of the kynurenine metabolism pathway, was upregulated in the hippocampus, prefrontal cortex, and amygdala of the Ox-treated mice 4 h after LPS administration. Based on these results, we suggest that early life stress from AD aggravates susceptibility to systemic inflammation in the adolescent brain, leading to depressive behaviors with abnormal kynurenine metabolism.

中文翻译：

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来自过敏性皮炎的早期生活压力通过神经炎症启动导致青春期雄性小鼠的抑郁样行为

过敏性皮炎 (AD) 与瘙痒和瘙痒相关，是生命早期的主要压力状况之一。AD 还通过神经免疫相互作用影响神经精神障碍和发育障碍的发生率。据我们所知，没有报告使用动物模型评估儿童早期皮炎对以后生活中精神疾病的影响。在这里，我们在雄性 C57BL/6J 小鼠的早期生命中开发了恶唑酮 (Ox) 诱导的 AD 模型，其耳朵从出生后天数 (PD) 2 到 PD30 反复受到 Ox 的挑战。在 PD30 中，Ox 处理的耳朵显着增厚，并显示出表皮增生以及耳组织中 T 辅助 2 细胞因子、白细胞介素 (IL)-4 和 IL-13 的表达增加。此外，Ox 处理的小鼠的血清免疫球蛋白 E 水平和血清皮质酮水平高于对照组小鼠。尽管 Ox 处理的 PD40 小鼠既没有表现出行为异常，也没有表现出大脑中促炎细胞因子表达的增加，但这项研究表明，它们在基础条件下杏仁核中的 CD200R1 表达下调，并且额外的脂多糖 (LPS) 给药诱导了神经炎症反应的增强因为启动效应伴随着杏仁核和海马中 Iba-1 阳性小胶质细胞的增加。此外，经 Ox 处理的 PD40 小鼠在 LPS 给药后 24 小时表现出类似抑郁的行为，而对照小鼠则没有。有趣的是，吲哚胺 2,3-双加氧酶和犬尿氨酸 3-单加氧酶的表达，LPS 给药后 4 小时，犬尿氨酸代谢途径的关键限速酶在 Ox 处理的小鼠的海马、前额叶皮层和杏仁核中上调。基于这些结果，我们认为来自 AD 的早期生活压力会加剧青少年大脑对全身炎症的易感性，导致犬尿氨酸代谢异常的抑郁行为。