A Drosophila model relevant to chemotherapy-related cognitive impairment.
A Drosophila model relevant to chemotherapy-related cognitive impairment.
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DOI：
10.1038/s41598-023-46616-9
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发表时间：
2023-11-07
影响因子：
4.6
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中科院分区：
文献类型：
--
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化疗相关认知障碍（CRCI）是治疗的常见不良反应，其特征是涉及包括记忆在内的多个认知领域的缺陷。尽管CRCI的发病率很高，并且预计在未来几十年癌症幸存者的数量会增加，但CRCI的病理生理机制仍然不完全清楚，这表明需要新的模型系统来研究CRCI。鉴于果蝇中强大的遗传方法和便捷的高通量筛选能力，我们的目标是验证与CRCI相关的果蝇模型。我们给成年果蝇使用顺铂、环磷酰胺和阿霉素等化疗药物。所有测试的化疗均观察到神经功能缺损，阿霉素，特别是顺铂也导致记忆缺损。然后，我们对顺铂治疗的果蝇组织进行了组织学和免疫组织化学分析，证明神经病理学证据表明神经变性，DNA损伤和氧化应激增加。因此，我们的与CRCI相关的果蝇模型概括了化疗患者的临床、放射学和组织学改变。我们的新果蝇模型可用于促进CRCI（以及更普遍的化疗诱导的神经毒性）通路的机制解剖和药物筛选，以确定疾病改善疗法。
Chemotherapy-related cognitive impairment (CRCI) is a common adverse effect of treatment and is characterized by deficits involving multiple cognitive domains including memory. Despite the significant morbidity of CRCI and the expected increase in cancer survivors over the coming decades, the pathophysiology of CRCI remains incompletely understood, highlighting the need for new model systems to study CRCI. Given the powerful array of genetic approaches and facile high throughput screening ability in Drosophila, our goal was to validate a Drosophila model relevant to CRCI. We administered the chemotherapeutic agents cisplatin, cyclophosphamide, and doxorubicin to adult Drosophila. Neurologic deficits were observed with all tested chemotherapies, with doxorubicin and in particular cisplatin also resulting in memory deficits. We then performed histologic and immunohistochemical analysis of cisplatin-treated Drosophila tissue, demonstrating neuropathologic evidence of increased neurodegeneration, DNA damage, and oxidative stress. Thus, our Drosophila model relevant to CRCI recapitulates clinical, radiologic, and histologic alterations reported in chemotherapy patients. Our new Drosophila model can be used for mechanistic dissection of pathways contributing to CRCI (and chemotherapy-induced neurotoxicity more generally) and pharmacologic screens to identify disease-modifying therapies.
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影响因子：
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作者：
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