{"id":528,"title":"Lead impairs long-term memory by disrupting mitochondrial redox homeostasis in Drosophila","title_zh":"铅暴露通过扰乱果蝇线粒体氧化还原稳态损害长期记忆","url":"https://doi.org/10.1073/pnas.2612578123","doi":"10.1073/pnas.2612578123","pmid":null,"journal":"Proceedings of the National Academy of Sciences","kind":"paper","lang":"en","published_at":"2026-11-04T00:00:00+00:00","fetched_at":"2026-11-08T03:45:22+00:00","authors":["Cheng-Tzu Hsu","Te-Wei Lu","Ya-Ting Yang","Chun-Chao Chen","Yen-Hua Chiu","Jung-Hsuan Yang","Zheng-Wen Wu","Wei-Kai Cheng","Jheng-Wei Wu","Chen-Hao Shiu","Sih-Kai Chuang","Kuan-Lin Feng","Hsuan-Wen Lin","Jia-Ling Yang","Ann-Shyn Chiang"],"primary_topic":"repro-aging","topics":[{"slug":"repro-aging","score":5.0,"hits":["mitochondria","mitochondrial"]},{"slug":"animal-models","score":3.2,"hits":["drosophila"]}],"topic_score":5.0,"preference_score":0.0,"preference_labels":[],"llm_score":47.0,"final_score":53.0,"score_dims":{"novelty":70,"rigor":75,"impact":30,"relevance":18,"translation":20},"recommend_reason":"机制研究设计扎实（遗传可操作果蝇模型、靶向氧化还原探针、抗氧化挽救实验），但研究对象为果蝇记忆的神经毒理，与生殖医学、配子与胚胎发育无直接关联，仅供关注环境毒物暴露与生殖/发育毒性交叉领域者作为背景参考。","keywords":["铅暴露","线粒体氧化还原","长期记忆","果蝇模型","神经毒性","EGCG"],"selected":0,"story_id":68,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-cns","source_name":"Crossref · CNS 与大子刊新上线（领域过滤）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"pnas","journal_tier":"general-top","journal_if":9.4,"is_mock":false,"summary_zh":"该研究以黑腹果蝇为模型，考察发育期与成体期铅暴露对记忆的影响。结果显示铅暴露选择性损害依赖蛋白质合成的长期记忆（LTM），而不影响其他记忆类型。利用线粒体靶向氧化还原生物传感器（mito-roGFP2-Orp1）发现，铅升高胆碱能神经元与背前侧（DAL）神经元的线粒体氧化应激、破坏氧化还原稳态，并抑制训练诱导的 DAL 神经元新生蛋白合成，从而阻碍记忆巩固；表没食子儿茶素没食子酸酯（EGCG）抗氧化处理可恢复氧化还原平衡并挽救 LTM。研究将线粒体氧化还原失调确定为连接环境铅暴露与记忆巩固障碍的关键机制，并提供可遗传操作的神经毒性研究平台。","summary":"Lead (Pb) exposure remains a major environmental risk factor for cognitive dysfunction, yet the cellular mechanisms underlying Pb-induced memory impairment are poorly understood. Here, we show that both developmental and adult-onset Pb exposure selectively disrupts protein-synthesis-dependent long-term memory (LTM) in Drosophila melanogaster while sparing other memory forms. Using a mitochondria-targeted redox biosensor (mito-roGFP2-Orp1), we found that Pb elevates mitochondrial oxidative stress and disrupts redox homeostasis in cholinergic neurons and in dorsal-anterior-lateral (DAL) neurons, a critical locus for LTM consolidation. Pb-induced redox imbalance suppresses training-induced de novo protein synthesis in DAL neurons, thereby impairing memory consolidation. Antioxidant treatment with epigallocatechin gallate restores mitochondrial redox balance and rescues LTM by reinstating activity-dependent protein synthesis in DAL neurons. These findings identify mitochondrial redox dysregulation as a key mechanism linking environmental Pb exposure to impaired memory consolidation. Our results further establish a genetically tractable platform for dissecting neurotoxic mechanisms and for evaluating antioxidant-based strategies to mitigate Pb-induced cognitive dysfunction.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}