Bisphenol-A exposure induced neurotoxicity and associated with synapse and cytoskeleton in Neuro-2a cells.

Bisphenol A (BPA) is an environmental chemical that induces neurotoxic effects for human. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic morphology. The stability of the cytoskeleton in nerve cells in the brain is regulated by Tau and MAP2. This study aimed to determine the toxicity of BPA to Neuro-2a cells by investigating the synaptic and cytoskeletal damage induced in these cells by 24 h of exposure to 0 (MEM), 50, 100, 150, or 200 μM BPA or DMSO. MTT and LDH assays showed that the death rates of Neuro-2a cells increased, as the BPA concentration increased. Ultrastructural assays revealed that cells underwent nucleolar swelling as well as nuclear membrane and partial mitochondrial dissolution or condensation, following BPA exposure. Morphological analysis further revealed that compared with the cells in the control group, the cells in the BPA-treated groups shrank, became rounded, and exhibited a reduced number of synapses. BPA also significantly decreased the relative protein and mRNA expression levels of Dbn, MAP2 and Tau (P < .01), but increased the relative protein and mRNA expression levels of SYP (P < .01). These results indicated that BPA suppressed the development and proliferation of Neuro-2a cells by disrupting cellular and synaptic integrity and inflicting cytoskeleton injury.