A Drosophila model relevant to chemotherapy-related cognitive impairment

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 pathop...

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Bibliographic Details
Published in:Scientific reports 2023-11, Vol.13 (1), p.19290-19290, Article 19290
Main Authors: Torre, Matthew, Bukhari, Hassan, Nithianandam, Vanitha, Zanella, Camila A., Mata, Douglas A., Feany, Mel B.
Format: Article
Language:English
Subjects:
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Adult
Animals
Antineoplastic Agents - adverse effects
Brain
Cancer
Chemotherapy
Chemotherapy-Related Cognitive Impairment
Cisplatin - adverse effects
Climbing
Cognitive ability
Cognitive Dysfunction - diagnosis
DNA damage
Doxorubicin - adverse effects
Drosophila
Humanities and Social Sciences
Humans
Insects
Memory
multidisciplinary
Neurodegeneration
Neuropathology
Neurotoxicity
Oxidative stress
Pathophysiology
Science
Science (multidisciplinary)
Statistical significance
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-46616-9