A Drosophila Model Relevant to Chemotherapy-Related Cognitive Impairment

Authors

• Matthew Torre
• Hassan Bukhari
• Vanitha Nithianandam
• Camila A Zanella
• Douglas A Mata
• Mel B Feany

Language

English

Publication Date

11-7-2023

Journal

Scientific Reports

DOI

10.1038/s41598-023-46616-9

PMID

37935827

PMCID

PMC10630312

PubMedCentral® Posted Date

11-7-2023

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Adult, Animals, Humans, Cisplatin, Antineoplastic Agents, Cognitive Dysfunction, Chemotherapy-Related Cognitive Impairment, Drosophila, Doxorubicin, Neurological disorders, Diseases of the nervous system

Published Open-Access

yes

Recommended Citation

Torre, Matthew; Bukhari, Hassan; Nithianandam, Vanitha; et al., "A Drosophila Model Relevant to Chemotherapy-Related Cognitive Impairment" (2023). Duncan NRI Faculty and Staff Publications. 246.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/246