Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations. Drosophila melanogaster as a model has been used in the present study to understand the involvement of Pb-induced oxidative stress in developing ASD behaviour. The larval feeding technique has been employed to administer different Pb concentrations (0.2–0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) antioxidants overexpressed or knockdown flies. Adult Drosophila (5-day old) were used for Pb content, biochemical, and behavioural analysis. Pb accumulated in the Drosophila brain induces oxidative stress and exhibited a human autistic-like behaviour such as reduced climbing, increased grooming, increased social spacing, and decreased learning and memory in a sex-specific manner. Pb-induced autistic-like behaviour was intensified in Sod or Cat-knockdown flies, whereas Sod or Cat-overexpressed flies overcome that behavioural alterations. These results unequivocally proved that Pb-induced oxidative stress causes ASD behaviour of humans in Drosophila. Thus, Drosophila is used as a model organism to analyse ASD-like human behaviour and underlines the importance of using antioxidant therapy in alleviating ASD symptoms in children.

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中文翻译：

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铅 (Pb) 诱导的氧化应激介导黑腹果蝇的性别特异性自闭症样行为

自闭症谱系障碍 (ASD) 是一种高度普遍的神经发育障碍，其特征在于三种主要的行为症状：异常的社交互动、语言和非语言交流障碍，以及重复和受限的活动或兴趣。尽管 ASD 的确切病因仍然未知，但研究表明遗传与环境污染物之间存在联系。环境污染物重金属铅 (Pb) 与 ASD 相关。铅也可能表现出性别特异性的 ASD 行为，正如在全球人口中所证明的那样。黑腹果蝇作为模型已在本研究中用于了解铅诱导的氧化应激在发展 ASD 行为中的作用。幼虫喂养技术已被用于向过表达或击倒果蝇的Oregon-R ( ORR )、超氧化物歧化酶 ( Sod ) 或过氧化氢酶 ( Cat ) 抗氧化剂施用不同的 Pb 浓度 (0.2–0.8 mM)。成年果蝇（5 天大）用于铅含量、生化和行为分析。铅在果蝇中积累大脑会诱发氧化应激并表现出人类自闭症的行为，例如减少攀爬、增加梳理毛发、增加社交距离以及以特定性别的方式减少学习和记忆。铅诱导的自闭症样行为在Sod或Cat敲低果蝇中得到加强，而Sod或Cat过度表达的果蝇克服了这种行为改变。这些结果明确证明，铅诱导的氧化应激会导致果蝇中人类的 ASD 行为。因此，果蝇被用作分析 ASD 样人类行为的模型生物，并强调了使用抗氧化疗法在缓解儿童 ASD 症状方面的重要性。

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