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孕期电子烟烟雾暴露对大鼠胎儿海马体中mTOR信号传导的影响。

Impact of e-cigarette vaping aerosol exposure in pregnancy on mTOR signaling in rat fetal hippocampus.

作者信息

Lee Jehoon, Orzabal Marcus R, Naik Vishal D, Ramadoss Jayanth

机构信息

Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, United States.

Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, School of Medicine, Wayne State University, Detroit, MI, United States.

出版信息

Front Neurosci. 2023 Jun 28;17:1217127. doi: 10.3389/fnins.2023.1217127. eCollection 2023.

Abstract

Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and many view them as less harmful and may help quit or reduce combustible cigarettes. Implementing a state-of-the-art engineered vaping system, comprising an atomizer similar to those sold in vape shops, we aimed to utilize a translational e-cig inhalation delivery method to provide crucial information on the impact of prenatal e-cig aerosols on the developing brain hippocampal mTOR system in a rat model system. Gestational e-cig vaping significantly increased P-mTOR levels ( < 0.05) in the rat fetal hippocampi in the nicotine group (comprising of VG/PG + nicotine) compared to the control and the juice (comprising of VG/PG) groups. Total mTOR expression was not different among groups. Immunofluorescence imaging demonstrated P-mTOR was detected exclusively in the granule cells of the dentate gyrus of the fetal hippocampus. E-cig did not alter DEPTOR, but RAPTOR and RICTOR were higher ( < 0.05) in the Nicotine group. Gestational e-cig vaping with nicotine increased ( < 0.05) the activity and expression of 4EBP1, p70S6K, but decreased ( < 0.05) P-PKCα in the fetal hippocampi. In summary, dysregulation of mTORC1 and the related mTORC2, their activity, and downstream proteins together may play a critical role in e-cig-vaping-induced neurobiological phenotypes during development.

摘要

近年来,孕期使用电子烟已成为一个主要的健康问题,许多人认为电子烟危害较小,可能有助于戒烟或减少可燃香烟的使用。我们采用了一种先进的工程化雾化系统,该系统包含一个与电子烟商店所售类似的雾化器,旨在利用一种转化型电子烟吸入给药方法,为大鼠模型系统中产前电子烟气溶胶对发育中的脑海马体mTOR系统的影响提供关键信息。与对照组和果汁组(由丙二醇/植物甘油组成)相比,尼古丁组(由丙二醇/植物甘油+尼古丁组成)孕期使用电子烟显著增加了大鼠胎儿海马体中磷酸化mTOR(P-mTOR)水平(<0.05)。各组间总mTOR表达无差异。免疫荧光成像显示,P-mTOR仅在胎儿海马体齿状回的颗粒细胞中被检测到。电子烟未改变DEPTDOR,但尼古丁组中RAPTOR和RICTOR水平较高(<0.05)。孕期使用含尼古丁的电子烟会增加(<0.05)胎儿海马体中4EBP1、p70S6K的活性和表达,但会降低(<0.05)胎儿海马体中磷酸化蛋白激酶Cα(P-PKCα)水平。总之,mTORC1和相关的mTORC2及其活性以及下游蛋白的失调可能在发育过程中电子烟雾化诱导的神经生物学表型中起关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f889/10337480/2ce71639812f/fnins-17-1217127-g001.jpg

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