期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2020.619199
关键词
oxycodone; electrophysiology; RNA-sequencing (RNA-Seq); Von Frey; proton magnetic resonance spectroscopy (1H-MRS)
资金
- NIH [5P20GM103427, 5P30CA036727, 5P30MH062261, DA049577, DA046284, DA042379, DA046852]
- Nebraska Research Initiative (NRI)
- National Institute for General Medical Science (NIGMS) [INBREP20GM103427-19]
- Fred & Pamela Buffett Cancer Center Support Grant [P30 CA036727]
Using a preclinical rodent model, the study investigated the impact of in utero and postnatal oxycodone exposure on offspring neurodevelopment and behavior. The findings indicated significant changes in key brain metabolites, synaptic currents, and gene expression associated with synaptic transmission, neurodevelopment, and addiction. Additionally, exposed offspring showed lower pain thresholds in adulthood, highlighting potential long-term developmental effects of opiates.
Background: Increased risk of oxycodone (oxy) dependency during pregnancy has been associated with altered behaviors and cognitive deficits in exposed offspring. However, a significant knowledge gap remains regarding the effect of in utero and postnatal exposure on neurodevelopment and subsequent behavioral outcomes. Methods: Using a preclinical rodent model that mimics oxy exposure in utero (IUO) and postnatally (PNO), we employed an integrative holistic systems biology approach encompassing proton magnetic resonance spectroscopy (H-1-MRS), electrophysiology, RNA-sequencing, and Von Frey pain testing to elucidate molecular and behavioral changes in the exposed offspring during early neurodevelopment as well as adulthood. Results: H-1-MRS studies revealed significant changes in key brain metabolites in the exposed offspring that were corroborated with changes in synaptic currents. Transcriptomic analysis employing RNA-sequencing identified alterations in the expression of pivotal genes associated with synaptic transmission, neurodevelopment, mood disorders, and addiction in the treatment groups. Furthermore, Von Frey analysis revealed lower pain thresholds in both exposed groups. Conclusions: Given the increased use of opiates, understanding the persistent developmental effects of these drugs on children will delineate potential risks associated with opiate use beyond the direct effects in pregnant women.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据