Chen Zhong, Chen Wanqiu, Li Yong, Moos Malcolm, Xiao Daliao, Wang Charles
Center for Genomics, School of Medicine, Loma Linda University, 11021 Campus St., Loma Linda, CA 92350, USA.
Lawrence D. Longo, MD Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.
iScience. 2022 Jun 30;25(8):104686. doi: 10.1016/j.isci.2022.104686. eCollection 2022 Aug 19.
Although emerging evidence reveals that vaping alters the function of the central nervous system, the effects of maternal vaping on offspring brain development remain elusive. Using a well-established exposure model, we performed single-nucleus ATAC-seq (snATAC-seq) and RNA sequencing (snRNA-seq) on prenatally e-cigarette-exposed rat brains. We found that maternal vaping distorted neuronal lineage differentiation in the neonatal brain by promoting excitatory neurons and inhibiting lateral ganglionic eminence-derived inhibitory neuronal differentiation. Moreover, maternal vaping disrupted calcium homeostasis, induced microglia cell death, and elevated susceptibility to cerebral ischemic injury in the developing brain of offspring. Our results suggest that the aberrant calcium signaling, diminished microglial population, and impaired microglia-neuron interaction may all contribute to the underlying mechanisms by which prenatal e-cigarette exposure impairs neonatal rat brain development. Our findings raise the concern that maternal vaping may cause adverse long-term brain damage to the offspring.
尽管新出现的证据表明吸电子烟会改变中枢神经系统的功能，但母亲吸电子烟对后代大脑发育的影响仍不清楚。我们使用一个成熟的暴露模型，对产前暴露于电子烟的大鼠大脑进行了单核染色质可及性测序（snATAC-seq）和RNA测序（snRNA-seq）。我们发现，母亲吸电子烟会通过促进兴奋性神经元和抑制外侧神经节隆起衍生的抑制性神经元分化，扭曲新生大脑中的神经元谱系分化。此外，母亲吸电子烟会破坏钙稳态，诱导小胶质细胞死亡，并增加后代发育中大脑对脑缺血损伤的易感性。我们的结果表明，异常的钙信号传导、小胶质细胞数量减少以及小胶质细胞与神经元相互作用受损，可能都有助于解释产前暴露于电子烟损害新生大鼠大脑发育的潜在机制。我们的研究结果引发了人们对母亲吸电子烟可能会给后代造成长期不良脑损伤的担忧。
