Bisphenol-A Exposure Induced Neurotoxicity and Synapse and Cytoskeleton Dysfunction in Neuro-2a Cells

Abstract

Bisphenol A (BPA) is one of the typical environmental endocrine disruptors. BPA was leached from polycarbonate containers into food and water, and it has been detected in collective samples from humans. Microtubule-associated protein 2 (MAP2) and Tau maintain microtubule normal function and promote the normal development of the nervous system. Synaptophysin (SYP) and drebrin (Dbn) proteins are involved in regulating synaptic plasticity. This study aimed to determine the adverse effects of BPA on Neuro-2a cells by investigating the synaptic and cytoskeletal damage. Cells were exposed to 0 (Minimum Essential Medium, MEM), 0.01% (v/v) DMSO and 150 µM BPA for 12, 24, or 36 h. Morphological analysis revealed that the cells in the BPA-treated groups shrank, collapsed, and had a reduced number of synapses compared with those in the control groups. CCK-8 and LDH assays showed that the mortality of Neuro-2a cells increased as the BPA treatment time was prolonged. Transmission electron microscopic analysis further revealed that cells demonstrated nucleolar swelling and nuclear membrane and partial mitochondrial dissolution or condensation following BPA exposure. BPA also significantly decreased the relative protein expression levels of MAP2, Tau, and Dbn (P < 0.01). Interestingly, the relative protein expression levels of SYP increased (P < 0.01). These results indicated that BPA damaged the development and proliferation of Neuro-2a cells by disrupting cytoskeleton and synaptic integrity.