Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
Biochem Pharmacol. 2020 Aug;178:114120. doi: 10.1016/j.bcp.2020.114120. Epub 2020 Jun 24.
As a stable environmental contaminant, nonylphenol (NP) has been shown to induce some neurological deficits in the cerebellum, although the underlying mechanism is still unknown. In the present study, we aimed to investigate the effects of perinatal exposure to NP on myelination, an important process essential for the intact cerebellar function, in the offspring cerebellum. Exposure to NP delayed the myelination in the offspring cerebellum during perinatal period. The myelination recovered in the cerebellum of offspring exposed to NP over time, and returned to normal in adulthood. In addition, perinatal exposure to NP reduced mature oligodendrocytes (myelin-forming glial cells) and increased astrocytes in the offspring cerebellum. BMP signaling is believed to negatively regulate oligodendrogliogenesis and myelination. In the present study, BMP4, p-Smad1/5, and ID4, key members of BMP signaling, were increased in the cerebellum of offspring exposed to NP. Taken together, these lines of evidence suggest that the activation of BMP signaling may underlie the decreased oligodendrogliogenesis and increased astrogliogenesis, and the consequent delay of myelination in the cerebellum of offspring perinatally exposed to NP.
作为一种稳定的环境污染物，壬基酚（NP）已被证明会在小脑引起一些神经功能缺陷，尽管其潜在机制尚不清楚。在本研究中，我们旨在研究围产期暴露于 NP 对后代小脑髓鞘形成的影响，髓鞘形成是小脑完整功能所必需的重要过程。NP 暴露会延迟后代小脑在围产期的髓鞘形成。随着时间的推移，NP 暴露的后代小脑中的髓鞘形成恢复正常，并在成年期恢复正常。此外，围产期暴露于 NP 会减少后代小脑中的成熟少突胶质细胞（形成髓鞘的神经胶质细胞）并增加星形胶质细胞。BMP 信号被认为可负向调节少突胶质细胞发生和髓鞘形成。在本研究中，NP 暴露后代小脑中的 BMP4、p-Smad1/5 和 ID4 等 BMP 信号的关键成员增加。总之，这些证据表明，BMP 信号的激活可能是 NP 围产期暴露后代小脑少突胶质细胞发生减少和星形胶质细胞发生增加，以及随后髓鞘形成延迟的基础。
