1. Academic Validation
  2. Bisphenol-A induces neurodegeneration through disturbance of intracellular calcium homeostasis in human embryonic stem cells-derived cortical neurons

Bisphenol-A induces neurodegeneration through disturbance of intracellular calcium homeostasis in human embryonic stem cells-derived cortical neurons

  • Chemosphere. 2019 Aug;229:618-630. doi: 10.1016/j.chemosphere.2019.04.099.
Hongou Wang 1 Peiqiang Zhao 1 Qiansheng Huang 2 Yulang Chi 3 Sijun Dong 4 Jianglin Fan 5
Affiliations

Affiliations

  • 1 Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 2 Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China.
  • 3 Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China. Electronic address: [email protected].
  • 4 Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China; Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021, China. Electronic address: [email protected].
  • 5 Department of Molecular Pathology, Faculty of Medicine, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.
Abstract

Bisphenol-A (BPA) is a representative exogenous endocrine disruptor, which is extensively composed in plastic products. Due to the capability of passing through the blood-brain barrier, evidence has linked BPA exposure with multiple neuropsychological dysfunctions, neurobehavioral disorders and neurodegenerative diseases. However, the underlying mechanism by which BPA induces neurodegeneration still remains unclear. Our study used human embryonic stem cells-derived human cortical neurons (hCNs) as a cellular model to investigate the adverse neurotoxic effects of BPA. hCNs were treated with 0, 0.1, 1 and 10 μM BPA for 14 days. Impacts of BPA exposure on cell morphology, cell viability and neural marker (MAP2) were measured for evaluating the neurodegeneration. The intracellular calcium homeostasis, Reactive Oxygen Species (ROS) generation and organelle functions were also taken into consideration. Results revealed that chronic exposure of BPA damaged the neural morphology, induced neuronal Apoptosis and decreased MAP2 expression at the level of both transcription and translation. The intracellular calcium levels were elevated in hCNs after BPA exposure through NMDARs-nNOS-PSD-95 mediating. Meanwhile, BPA led to oxidative stress by raising the ROS generation and attenuating the antioxidant defense in hCNs. Furthermore, BPA triggered ER stress and increased cytochrome c release by impairing the mitochondrial function. Ultimately, BPA triggered the cell Apoptosis by regulating Bcl-2 Family and caspase-dependent signaling pathway. Taken together, BPA exerted neurotoxic effects on hCNs by eliciting Apoptosis, which might due to the intracellular calcium homeostasis perturbation and cell organellar dysfunction.

Keywords

Apoptosis; Bisphenol-A; Calcium homeostasis perturbation; Cell organelles dysfunctions; Neurodegeneration; hESC-derived cortical neurons.

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