A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior.
A Holistic Systems Approach to Characterize the Impact of Pre- and Post-natal Oxycodone Exposure on Neurodevelopment and Behavior.
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DOI：
10.3389/fcell.2020.619199
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发表时间：
2020
影响因子：
5.5
通讯作者：
Yelamanchili SV
中科院分区：
文献类型：
--
作者：
Odegaard KE;Schaal VL;Clark AR;Koul S;Sankarasubramanian J;Xia Z;Mellon M;Uberti M;Liu Y;Stothert A;Van Hook M;Wang H;Guda C;Lisco SJ;Pendyala G;Yelamanchili SV
背景资料：妊娠期间羟考酮（oxy）依赖性风险增加与暴露后代的行为改变和认知缺陷相关。然而，关于宫内和产后暴露对神经发育和随后的行为结果的影响，仍然存在重大的知识差距。研究方法：使用临床前啮齿动物模型，模拟氧暴露在子宫内（IUO）和出生后（PNO），我们采用了一个综合的整体系统生物学方法，包括质子磁共振波谱（1H-MRS），电生理学，RNA测序，和Von Frey疼痛测试，以阐明暴露的后代在早期神经发育以及成年期的分子和行为变化。结果如下：1H-MRS研究揭示了暴露后代中关键脑代谢物的显著变化，这与突触电流的变化相证实。采用RNA测序的转录组学分析确定了治疗组中与突触传递、神经发育、情绪障碍和成瘾相关的关键基因表达的改变。此外，Von Frey分析显示两个暴露组的疼痛阈值较低。结论：鉴于阿片类药物使用的增加，了解这些药物对儿童的持续发育影响将揭示与阿片类药物使用相关的潜在风险，而不仅仅是对孕妇的直接影响。
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 (1H-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: 1H-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.
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影响因子：
2.7
作者：
Nie JJ;Sun S;Huang SQ
通讯作者：
Huang SQ
具有滥用责任的鸦片药物劫持了内源性阿片类药物系统，以破坏中枢神经系统中的神经元和神经胶质成熟。
影响因子：
2.6
作者：
Hauser KF;Knapp PE
通讯作者：
Knapp PE
影响因子：
7.4
作者：
Byrnes EM;Vassoler FM
通讯作者：
Vassoler FM
影响因子：
4.7
作者：
Ballini, Chiara;Della Corte, Laura;Giovannini, Maria Grazia
通讯作者：
Giovannini, Maria Grazia
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J