Chemotherapy-induced cognitive impairment (CICI): Cisplatin's effects on neurotransmitter regulation and oxidative stress in Drosophila melanogaster

Chemotherapy-induced cognitive impairment (CICI), commonly known as “chemo brain,” is a significant and persistent complication of cancer therapy, characterized by memory deficits and broader cognitive dysfunction. Despite its prevalence among cancer survivors, the underlying neurotoxic mechanisms remain incompletely understood. In this study, we utilized Drosophila melanogaster as a model organism to systematically investigate the neurobiological effects of cisplatin, a widely used platinum-based chemotherapeutic agent. Cisplatin exposure led to a marked reduction in lifespan and impaired locomotor function, indicating pronounced neurotoxicity. Biochemical analyses demonstrated dose-dependent disruptions in oxidative stress parameters - such as superoxide dismutase, catalase, glutathione, and total antioxidant capacity- alongside elevated reactive oxygen species and pro-apoptotic gene expression within neural tissues. Furthermore, cisplatin altered the synthesis and regulation of key neurotransmitters, including acetylcholine, GABA, dopamine, and serotonin. Collectively, these findings establish Drosophila as a robust, translationally relevant model for elucidating the molecular pathways of CICI and for high-throughput screening of neuroprotective interventions.