Differential regulations of neural activity and survival in primary cortical neurons by PFOA or PFHpA

Perfluorinated compounds (PFCs), organofluoride compounds comprising carbon–fluorine and carbon–carbon bonds, are used as water and oil repellents in textiles and pharmaceutical tablets; however, they are associated with potential neurotoxic effects. Moreover, the impact of PFCs on neuronal survival, activity, and regulation within the brain remains unclear. Additionally, the mechanisms through which PFCs induce neuronal toxicity are not well-understood because of the paucity of data. This study elucidates that perfluorooctanoic acid (PFOA) and perfluoroheptanoic acid (PFHpA) exert differential effects on the survival and activity of primary cortical neurons. Although PFOA triggers apoptosis in cortical neurons, PFHpA does not exhibit this effect. Instead, PFHpA modifies dendritic spine morphogenesis and synapse formation in primary cortical neuronal cultures, additionally enhancing neural activity and synaptic transmission. This research uncovers a novel mechanism through which PFCs (PFHpA and PFOA) cause distinct alterations in dendritic spine morphogenesis and synaptic activity, shedding light on the molecular basis for the atypical behaviors noted following PFC exposure. Understanding the distinct effects of PFHpA and PFOA could guide regulatory policies on PFC usage and inform clinical approaches to mitigate their neurotoxic effects, especially in vulnerable population. [Display omitted] •PFOA induces cortical neuron apoptosis.•PFHpA induces spontaneous neural network activity in cortical neuron cultures.•PFCs (PFHpA or PFOA) affect dendritic spine and synapse formation in cortical neuron cultures.•PFC exposure differentially changes gene expression in primary cortical neurons.