Analyzing Cadmium-Driven Biochemical Changes: a Multi-Disciplinary Approach for the Evaluation of Neuron and Microglia Models

Introduction: Cadmium is a highly toxic, non-essential heavy metal that accumulates in the human body, leading to severe neurotoxicity. It enters the central nervous system through the olfactory nerves or by increasing blood brain barrier permeability. Cadmium bioaccumulation triggers oxidative stress, which fuels neuroinflammatory pathways linked to neurodegenerative disorders. Understanding these metal-driven molecular alterations is critical for clarifying the mechanisms of cellular harm.

Methods: Human neuroblastoma SH-SY5Y cells have been used to investigate the impacts of cadmium on both the process of neuronal differentiation as well as on fully differentiated neuronal-like cells. In this study biochemical approaches were coupled with Fourier Transform Infrared (FTIR) microspectroscopy as a marker-free, non-destructive method to obtain an unbiased look at the cellular biochemical profile.

Results: By merging biochemical data and micro-FTIR spectroscopic data with advanced machine learning algorithms, the study shows the modifications in physicochemical properties of lipids induced by cadmium exposure during the differentiation process; in fact cadmium alters membrane lipid composition, which leads to alteration in neurite outgrowth. Moreover there is a reduction in carnitin and cardiolipin content paired with a lower mitochondrial respiration and ATP production in cadmium-differentiating cells.

Conclusions: Pairing non-destructive spectroscopic insights with supportive biochemical and omics analyses clarified cadmium impact on neuronal differentiation, also this multi-disciplinary approach allows to understand the molecular pathways responsible for cadmium-induced cellular damage.