Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder which manifests itself in early childhood and is distinguished by recurring behavioral patterns, and dysfunction in social/communication skills. Ubiquitous environmental pollutant, di-2-ethylhexyl phthalate (DEHP) is one of the most frequently used plasticizers in various industrial products, e.g. vinyl flooring, plastic toys, and medical appliances. DEHP gets easily released into the environment and leads to human exposure through various routes. DEHP has been described to be linked with oxidative stress in various organs in animal/human studies. Increased concentration of DEHP has also been detected in ASD children which indicates an association between phthalates exposure and ASD. However, effect of DEHP on autism-like behavior has not been investigated previously. Therefore, this study probed the effect of DEHP on autism-like behavior (marble burying, self-grooming and sociability) and innate immune cells (dendritic cells/neutrophils)/cerebellar oxidant-antioxidant balance (NFkB, iNOS, NADPH oxidase, nitrotyrosine, lipid peroxides, Nrf2, SOD, GPx) in BTBR and C57 mice. Our data show that DEHP treatment causes worsening of autism-like behavior in BTBR mice which is associated with enhancement of oxidative stress in innate immune cells and cerebellum with concomitant lack of antioxidant protection. DEHP also causes oxidative stress in C57 mice in both innate immune cells and cerebellar compartment, however there is Nrf2-mediated induction of enzymatic antioxidants which protects them from upregulated oxidative stress. This proposes the notion that ubiquitous environmental pollutants such as DEHP may be involved in the pathogenesis/progression of ASD through dysregulation of antioxidant-antioxidant balance in innate immune cells and cerebellum.

自闭症谱系障碍 (ASD) 是一种复杂的神经发育障碍，在儿童早期表现出来，其特征是反复出现的行为模式和社交/沟通技能功能障碍。邻苯二甲酸二-2-乙基己酯（DEHP）是一种普遍存在的环境污染物，是乙烯基地板、塑料玩具和医疗器械等各种工业产品中最常用的增塑剂之一。 DEHP 很容易释放到环境中，并通过多种途径导致人类接触。在动物/人类研究中，DEHP 被描述为与多种器官的氧化应激有关。自闭症谱系障碍 (ASD) 儿童中也检测到 DEHP 浓度升高，这表明邻苯二甲酸盐暴露与自闭症谱系障碍 (ASD) 之间存在关联。然而，DEHP 对自闭症样行为的影响此前尚未被研究过。因此，本研究探讨了 DEHP 对自闭症样行为（大理石埋葬、自我修饰和社交能力）和先天免疫细胞（树突状细胞/中性粒细胞）/小脑氧化剂-抗氧化剂平衡（NF k B、iNOS、NADPH 氧化酶、 BTBR 和 C57 小鼠中的硝基酪氨酸、脂质过氧化物、Nrf2、SOD、GPx）。我们的数据表明，DEHP 治疗会导致 BTBR 小鼠的自闭症样行为恶化，这与先天免疫细胞和小脑的氧化应激增强有关，同时缺乏抗氧化保护。 DEHP 还会在 C57 小鼠的先天免疫细胞和小脑室中引起氧化应激，但是 Nrf2 介导的酶抗氧化剂的诱导可以保护它们免受氧化应激上调的影响。 这提出了这样一种观点，即 DEHP 等普遍存在的环境污染物可能通过先天免疫细胞和小脑中抗氧化-抗氧化平衡失调参与 ASD 的发病/进展。