Zhao, M., et al. Proteomic profiling of primary astrocytes and co-cultured astrocytes/microglia exposed to acrylamide, 75, 78-88

Acrylamide (AA) is a common food contaminant known to detrimentally affect the nervous system. Homeostasis of the nervous system is dependent on glial cells, namely astrocytes and microglia, which actively participate in neuronal survival signaling pathways. Although the differential responses of monocultured astrocytes compared to co-cultured astrocytes and microglia to AA exposure have been investigated, the global effects and potential molecular mechanism involved in AA-induced neurotoxicity remain unknown. In this study, the impacts of AA on primary monocultured astrocytes and co-cultured astrocytes with microglia were determined using Orbitrap-based proteomic analysis. The results showed that AA exposure mainly caused disruption of cellular and metabolic processes, biological regulation, and cell development. Furthermore, oxidative stress-related pathways and immune responses were the main regulatory functions influenced by AA-induced neurotoxicity. Additionally, Nrf2 and other downstream proteins in the oxidative stress-related pathway were up-regulated. There were significant differences between the protein changes in the monocultured astrocytes and co-cultured astrocytes with microglia, indicating that AA affected cell-cell communication between astrocytes and microglia. Overall, these findings illustrate the global effects of AA-induced functionality and pathway alteration and their involvement in the development of neurological deficits in primary glial cell cultures. These findings may provide new insights for the development of a pathway approach suitable for the risk assessment of AA.