Electrochemistry Meets Omics: Charting the Path to Prevent Chemotherapy-Induced Cognitive Decline

Chemotherapy-induced cognitive decline (“chemobrain”) is a major complication faced by cancer survivors, manifesting as persistent deficits in memory, learning, attention, and motor function. Despite its prevalence and profound impact on quality of life, no approved preventative strategies exist. A central challenge is that the molecular and neurochemical underpinnings of chemobrain remain poorly defined, leaving the field without a clear mechanistic framework to guide treatment development.

To address this gap, we employed zebrafish (Danio rerio) as a versatile model system to characterize chemobrain across molecular, neurochemical, and behavioral dimensions. Fast-scan cyclic voltammetry enabled real-time monitoring of dopamine, a neurotransmitter strongly implicated in cognitive impairment, which we correlated with learning and locomotor performance in behavioral assays. Complementary proteomic and lipidomic profiling using high-resolution mass spectrometry revealed widespread dysregulation in pathways linked to synaptic signaling, neuroinflammation, neuronal development, and lipid metabolism. Together, these approaches establish an integrative framework that connects molecular changes to neurochemical and behavioral outcomes.

Building on these findings, we further identified L-carnosine, a naturally occurring dipeptide, as a promising preventative agent. Pretreatment with carnosine not only rescued behavioral impairments but also restored dopamine dynamics and reversed proteomic and lipidomic disturbances. Here, we will discuss how integrating electrochemical, behavioral, and multi-omics methodologies in a zebrafish model provides a comprehensive strategy for defining the molecular basis of chemobrain. Ultimately, our results highlight carnosine as a compelling candidate for preventing chemotherapy-induced cognitive decline.