Department of Anesthesiology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Cells. 2022 May 25;11(11):1740. doi: 10.3390/cells11111740.
The current opioid crisis, which has ravaged all segments of society, continues to pose a rising public health concern. Importantly, dependency on prescription opioids such as oxycodone (oxy) during and after pregnancy can significantly impact the overall brain development of the exposed offspring, especially at the synapse. A significant knowledge gap that remains is identifying distinct synaptic signatures associated with these exposed offspring. Accordingly, the overall goal of this current study was to identify distinct synaptic vesicle (SV) proteins as signatures for offspring exposed to oxy in utero (IUO) and postnatally (PNO). Using a preclinical animal model that imitates oxycodone exposure in utero (IUO) and postnatally (PNO), we used a quantitative mass spectrometry-based proteomics platform to examine changes in the synaptic vesicle proteome on post-natal day 14 (P14) IUO and PNO offspring. We identified MEGF8, associated with carpenter syndrome, to be downregulated in the IUO offspring while LAMTOR4, associated with the regulator complex involved in lysosomal signaling and trafficking, was found to be upregulated in the PNO groups, respectively. Their respective differential expression was further validated by Western blot. In summary, our current study shows exposure to oxy in utero and postnatally can impact the SV proteome in the exposed offspring and the identification of these distinct SV signatures could further pave the way to further elucidate their downstream mechanisms including developing them as potential therapeutic targets.
当前，阿片类药物危机肆虐社会各个阶层，继续对公共健康构成日益严重的威胁。重要的是，孕妇和产后依赖处方类阿片（如羟考酮）会严重影响暴露后代的整体大脑发育，尤其是在突触水平。目前仍存在一个显著的知识空白，即确定与这些暴露后代相关的独特突触特征。因此，本研究的总体目标是确定与宫内（IUO）和产后（PNO）暴露于羟考酮的后代相关的独特突触小泡（SV）蛋白作为特征。本研究使用一种模拟宫内（IUO）和产后（PNO）羟考酮暴露的临床前动物模型，使用基于定量质谱的蛋白质组学平台，检测产后第 14 天（P14）IUO 和 PNO 后代中突触小体蛋白组的变化。我们发现，与 Carpenter 综合征相关的 MEGF8 在 IUO 后代中下调，而与参与溶酶体信号转导和运输的调节复合物相关的 LAMTOR4 在 PNO 组中上调。Western blot 进一步验证了它们各自的差异表达。总之，本研究表明，宫内和产后暴露于羟考酮会影响暴露后代的 SV 蛋白质组，鉴定这些独特的 SV 特征可能进一步为阐明其下游机制铺平道路，包括将其开发为潜在的治疗靶点。
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