Cell Shocked: Investigating the Dose-Dependent Effects of Bisphenol-A Exposure on Murine Neural Cells, A Multi-Omics Analysis

Abstract

Bisphenol A (BPA), an endocrine-disrupting chemical found in numerous consumer products, has raised concerns about its potential neurotoxicity. We employed an integrative multi-omics approach, using the Neuro-2a mouse neuroblastoma cell line, to investigate the neurotoxic effects of BPA at human-relevant concentrations. This pilot study specifically aimed to determine biologically relevant doses of BPA for the Neuro2a model and characterize an in-vitro neurotoxicity profile. Initial findings indicated that high-dose BPA (100-500 µM) induced significant cytotoxicity, while lower doses (0.1-1 nM), representative of human exposure levels, did not significantly impact cell growth. Metabolomic analysis of chronic BPA exposure at such low doses revealed significant disruptions in energy homeostasis and lipid metabolism. Transcriptomic analysis of chronic low-dose BPA exposures similarly implicated genes involved in metabolic pathways, as well as in methylation and Wnt signaling. In conjunction, these findings highlight potential risk factors for neurological dysfunction and potentially neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease given similarly implicated dysregulation in these pathways. Overall, our findings support the idea that BPA may be a significant risk factor for neurological dysfunction and potentially neurodegenerative disorders by affecting key metabolic pathways, even at low, human relevant doses. The final aim of this work was to analyze EDC exposure as a mechanism of environmental racism and slow violence, drawing upon a specific case study involving Indigenous communities living near the Athabasca tar sands region of Alberta, Canada.