MiR-222-3p regulates methamphetamine-induced behavioral sensitization through PP2A–AKT signaling pathway in the dorsal striatum of male mice

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-03-01 DOI:10.1016/j.neulet.2025.138181

Gang Chen , Xingyao Chen , Wei Han , Baoyao Gao , Min Liang , Tao Li , Xinshe Liu

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引用次数: 0

Abstract

Drug addiction is a chronic and recurrent brain disease. Our previous research demonstrated that the B subunit of phosphatase 2A (PP2A/B) increased in the dorsal striatum (DS) of methamphetamine (METH)-sensitized mice. Interestingly, studies indicate that PP2A/B can also interplay with microRNA (miRNA). In this study, we investigated seven miRNAs that have been reported to potentially interplay with PP2A/B, and our results showed that miR-222-3p significantly decreased in the DS of METH-sensitized mice. We further used dual-luciferase reporter assay to clarify the regulatory relationship between miR-222-3p and PP2A/B mRNA, and we also constructed adeno-associated virus (AAV) to overexpress miR-222-3p in the DS to further examine the influence of miR-222-3p on METH-induced behavioral sensitization. Our results demonstrated that miR-222-3p did interplay with PP2A/B mRNA and overexpressed miR-222-3p could significant attenuate METH-induced behavioral sensitization. At the same time, overexpressed miR-222-3p could reverse the change in the PP2A–AKT signaling pathway in the DS of METH-sensitized mice. Our results indicate that overexpression of miR-222-3p in the DS might attenuate METH-induced behavioral sensitization through the PP2A–AKT signaling pathway.

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MiR-222-3p通过PP2A-AKT信号通路调节雄性小鼠背侧纹状体中甲基苯丙胺诱导的行为致敏。

药物成瘾是一种慢性反复发作的脑部疾病。我们之前的研究表明，甲基安非他明（METH）致敏小鼠背纹状体（DS）中磷酸酶2A （PP2A/B）的B亚基增加。有趣的是，研究表明PP2A/B也可以与microRNA （miRNA）相互作用。在这项研究中，我们研究了已经报道的七种可能与PP2A/B相互作用的miRNAs，我们的结果显示，在甲基甲醚致敏小鼠的DS中，miR-222-3p显著降低。我们进一步利用双荧光素酶报告基因法阐明miR-222-3p与PP2A/B mRNA之间的调控关系，并构建腺相关病毒（adeno-associated virus， AAV）在DS中过表达miR-222-3p，进一步研究miR-222-3p对甲基甲醚诱导的行为致敏的影响。我们的研究结果表明，miR-222-3p确实与PP2A/B mRNA相互作用，过表达的miR-222-3p可以显著减弱甲基醚诱导的行为致敏。同时，过表达miR-222-3p可以逆转甲基醚致敏小鼠DS中PP2A-AKT信号通路的变化。我们的研究结果表明，在DS中过表达miR-222-3p可能通过PP2A-AKT信号通路减弱meth诱导的行为致敏。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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