Effects of Environmentally Relevant Pharmaceuticals on Neurite Degeneration in SH-SY5Y Cells: Implications for Alzheimer's Disease

Sammanfattning

The increasing presence of pharmaceuticals in the environment has raised concerns regarding their potential effects on neuronal function and neurodegenerative processes associated with Alzheimer's disease. Neuritic degeneration and synaptic dysfunction are early pathological features of Alzheimer’s disease and contribute to impaired neuronal connectivity and cognitive decline. This study aimed to evaluate the effects of selected pharmaceuticals on neuronal viability and morphology using differentiated SH-SY5Y cells. Cells were exposed for 24 h to gemfibrozil, diphenhydramine hydrochloride, citalopram hydrobromide, propranolol hydrochloride, carbamazepine, and salbutamol across a range of concentrations. Cell viability was assessed using the AlamarBlue assay, while neuritic degeneration, process per cell, and branching were quantified using fluorescence-based imaging. Statistical analysis was performed using the Kruskal-Wallis test followed by Dunn’s post hoc test. No statistically significant effects were observed for most compounds across the measured endpoints. However, carbamazepine exposure resulted in a significant decrease in process per cell at the highest concentration (50 µM) (p = 0.0219). Additionally, non-significant tendencies towards reduced neuritic parameters were observed for several compounds, particularly diphenhydramine and citalopram. Overall, the results suggest that the tested pharmaceuticals exert limited effects on cell viability and neuronal morphology under the experimental conditions. However, the observed effects of carbamazepine on neuronal processes highlight the importance of further investigating how pharmaceutical exposure may influence neuronal structure and pathways relevant to neurodegeneration.