Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh (U.P.), India; Department of Biochemistry, School of Dental Sciences, Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 226 028, U.P., India.
Developmental Toxicology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh (U.P.), India; Academy of Scientific and Innovative Research (AcSIR), CSIR-IITR Lucknow Campus, Lucknow, India.
J Hazard Mater. 2020 Jun 15;392:122052. doi: 10.1016/j.jhazmat.2020.122052. Epub 2020 Jan 8.
CNS myelination process involves proliferation and differentiation of oligodendrocyte progenitor cells (OPCs). Defective myelination causes onset of neurological disorders. Bisphenol-A (BPA), a component of plastic items, exerts adverse effects on human health. Our previous studies indicated that BPA impairs neurogenesis and myelination process stimulating cognitive dysfunctions. But, the underlying mechanism(s) of BPA induced de-myelination and probable neuroprotection by curcumin remains elusive. We found that curcumin protected BPA mediated adverse effects on oligosphere growth kinetics. Curcumin significantly improved proliferation and differentiation of OPCs upon BPA exposure both in-vitro and in-vivo. Curcumin enhanced the mRNA expression and protein levels of myelination markers in BPA treated rat hippocampus. Curcumin improved myelination potential via increasing β-III tubulin-/MBP cells (neuron-oligodendrocyte co-culture) and augmented fluoromyelin intensity and neurofilament/MBP neurons in vivo. In silico docking studies suggested Notch pathway genes (Notch-1, Hes-1 and Mib-1) as potential targets of BPA and curcumin. Curcumin reversed BPA mediated myelination inhibition via increasing the Notch pathway gene expression. Genetic and pharmacological Notch pathway inhibition by DAPT and Notch-1 siRNA exhibited decreased curcumin mediated neuroprotection. Curcumin improved BPA mediated myelin sheath degeneration and neurobehavioral impairments. Altogether, results suggest that curcumin protected BPA induced de-myelination and behavioural deficits through Notch pathway activation.
中枢神经系统髓鞘形成过程涉及少突胶质前体细胞（OPC）的增殖和分化。髓鞘形成缺陷会导致神经紊乱的发生。双酚 A（BPA）是塑料制品的一种成分，对人类健康有不良影响。我们之前的研究表明，BPA 会损害神经发生和髓鞘形成过程，从而刺激认知功能障碍。但是，BPA 诱导脱髓鞘的潜在机制以及姜黄素可能的神经保护作用仍不清楚。我们发现姜黄素可保护 BPA 对寡球体生长动力学的不良影响。姜黄素在体外和体内均显著改善了 BPA 暴露时 OPC 的增殖和分化。姜黄素增强了 BPA 处理大鼠海马中髓鞘形成标志物的 mRNA 表达和蛋白水平。姜黄素通过增加β-III 微管蛋白/MBP 细胞（神经元-少突胶质细胞共培养）和体内增加氟髓磷脂强度和神经丝/MBP 神经元来提高髓鞘形成潜力。计算机对接研究表明 Notch 通路基因（Notch-1、Hes-1 和 Mib-1）是 BPA 和姜黄素的潜在靶点。姜黄素通过增加 Notch 通路基因表达逆转了 BPA 介导的髓鞘抑制。DAPT 和 Notch-1 siRNA 的遗传和药理学 Notch 通路抑制表现出姜黄素介导的神经保护作用降低。姜黄素改善了 BPA 介导的髓鞘鞘退化和神经行为损伤。总的来说，结果表明姜黄素通过激活 Notch 通路来保护 BPA 诱导的脱髓鞘和行为缺陷。
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