Exploratory Gene Expression Profiling of Cisplatin-Induced Neurotoxicity in Rat Brain

TL;DR

This study explores how cisplatin chemotherapy affects gene activity in rat brains, revealing potential molecular pathways linked to neurotoxicity and possible targets for neuroprotection.

Contribution

The study provides a novel transcriptomic map of cisplatin-induced neurotoxicity in rat brains and links findings to human glioma datasets for translational insights.

Findings

Cisplatin alters pathways related to synaptic signaling, neuroplasticity, and cellular metabolism in rat brains.

Key cisplatin-regulated genes correlate with prognosis and immune infiltration in human lower-grade gliomas.

The study identifies candidate targets for future neuroprotective strategies against cisplatin-induced neurotoxicity.

Abstract

Cisplatin is a widely used antineoplastic agent whose therapeutic efficacy is often limited by its adverse effects on the central nervous system. In this exploratory study, we characterized the transcriptomic impact of a cumulative cisplatin regimen on the male Wistar rat brain using microarray technology. Differentially expressed genes were identified, and their functional roles were investigated through enrichment analyses (KEGG) and Gene Ontology (GO), and the construction of protein–protein interaction (PPI) networks. Our results revealed significant alterations in pathways related to synaptic signaling, neuroplasticity, and cellular metabolism. To generate translational hypotheses, these findings were subsequently correlated in silico with public human lower-grade glioma (LGG) datasets, which suggested a potential association between key cisplatin-regulated genes and clinical prognosis and immune cell infiltration patterns. This manuscript does not include RT-qPCR (or Western blot) validation; results should be interpreted as hypothesis-generating and require orthogonal confirmation. These findings provide a comprehensive transcriptomic map of cisplatin-induced neurotoxicity, offering novel insights into its underlying molecular mechanisms and identifying a rich set of candidate targets for future neuroprotective strategies.

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