Effect of Combined Methamphetamine and Oxycodone Use on the Synaptic Proteome in an In Vitro Model of Polysubstance Use.
Effect of Combined Methamphetamine and Oxycodone Use on the Synaptic Proteome in an In Vitro Model of Polysubstance Use.
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多物质使用（PSU）通常涉及同时使用阿片类药物沿着兴奋剂。近年来，这一问题已升级为全国性的流行病。了解这些药物之间相互作用的机制和影响对于开发成瘾者的治疗方法至关重要。目前，PSU对突触（神经元之间的关键接触点）的影响仍然知之甚少。使用原代神经元的体外模型，我们研究了精神兴奋剂甲基苯丙胺（METH）和处方阿片类药物羟考酮（oxy）对突触蛋白质组的联合作用，使用基于定量质谱的蛋白质组学。进一步的CNOGO分析和免疫途径分析（IPA）表明，与神经可塑性和结构发育相关的几种分子功能，生物学过程和途径的失调。我们确定了一个关键的突触蛋白，Striatin-1，它在许多这些过程和功能中起着至关重要的作用，在METH+oxy处理后下调。Striatin-1的这种下调进一步通过Western blot验证。总体而言，本研究表明METH和oxy联合使用对神经功能的几种破坏性影响，并需要进一步详细研究导致突触功能障碍的机制。
Polysubstance use (PSU) generally involves the simultaneous use of an opioid along with a stimulant. In recent years, this problem has escalated into a nationwide epidemic. Understanding the mechanisms and effects underlying the interaction between these drugs is essential for the development of treatments for those suffering from addiction. Currently, the effect of PSU on synapses—critical points of contact between neurons—remains poorly understood. Using an in vitro model of primary neurons, we examined the combined effects of the psychostimulant methamphetamine (METH) and the prescription opioid oxycodone (oxy) on the synaptic proteome using quantitative mass-spectrometry-based proteomics. A further ClueGO analysis and Ingenuity Pathway Analysis (IPA) indicated the dysregulation of several molecular functions, biological processes, and pathways associated with neural plasticity and structural development. We identified one key synaptic protein, Striatin-1, which plays a vital role in many of these processes and functions, to be downregulated following METH+oxy treatment. This downregulation of Striatin-1 was further validated by Western blot. Overall, the present study indicates several damaging effects of the combined use of METH and oxy on neural function and warrants further detailed investigation into mechanisms contributing to synaptic dysfunction.
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影响因子：
2.7
作者：
Badiani, A;Oates, MM;Robinson, TE
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