Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the dorsomedial prefrontal cortex of male and female rats.
Repeated morphine exposure activates synaptogenesis and other neuroplasticity-related gene networks in the dorsomedial prefrontal cortex of male and female rats.
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DOI：
10.1016/j.drugalcdep.2021.108598
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发表时间：
2021-04-01
影响因子：
4.2
通讯作者：
Gewirtz JC
中科院分区：
文献类型：
--
作者：
Liu SX;Gades MS;Swain Y;Ramakrishnan A;Harris AC;Tran PV;Gewirtz JC
阿片类药物滥用是一种慢性疾病，可能涉及稳定的神经可塑性改变。虽然已经确定了一些有助于这些变化的分子，但受重复阿片类药物给药影响的更广泛的基因和基因网络仍然没有得到充分研究。我们采用下一代RNA测序（RNA-seq），然后定量染色质免疫沉淀，以研究成年雄性和雌性大鼠的背内侧前额叶皮层（dmPFC）的基因表达及其调节的变化后，每天注射吗啡（5.0 mg/kg; 10天）。免疫途径分析（IPA）用于分析受影响的分子途径，基因网络和相关的调控因子。一项补充的行为研究评估了相同的吗啡注射方案对自发活动、疼痛敏感性和躯体戒断体征的影响。行为上，重复注射吗啡诱导运动过度活跃和痛觉过敏的性别。在吗啡处理的大鼠中，90%的差异表达基因（DEG）在雄性和雌性中均上调，性别之间有35%的重叠。大量DEG在突触信号传导和神经可塑性中发挥作用。染色质免疫沉淀显示富集H3乙酰化，转录激活染色质标记。虽然大致相似，但在女性和男性中富集的基因本体网络中揭示了一些差异。我们的研究结果与先前基于先验基因选择的研究结果一致。我们的研究结果还揭示了新的基因和分子途径，这些基因和分子途径被反复的吗啡暴露上调，其中一些是男性和女性共有的，另一些是性别特异性的。
Opioid abuse is a chronic disorder likely involving stable neuroplastic modifications. While a number of molecules contributing to these changes have been identified, the broader spectrum of genes and gene networks that are affected by repeated opioid administration remain understudied. We employed Next-Generation RNA-sequencing (RNA-seq) followed by quantitative chromatin immunoprecipitation to investigate changes in gene expression and their regulation in adult male and female rats’ dorsomedial prefrontal cortex (dmPFC) after a regimen of daily injection of morphine (5.0 mg/kg; 10 days). Ingenuity Pathway Analysis (IPA) was used to analyze affected molecular pathways, gene networks, and associated regulatory factors. A complementary behavioral study evaluated the effects of the same morphine injection regimen on locomotor activity, pain sensitivity, and somatic withdrawal signs. Behaviorally, repeated morphine injection induced locomotor hyperactivity and hyperalgesia in both sexes. 90% of differentially expressed genes (DEGs) in morphine-treated rats were upregulated in both males and females, with a 35% overlap between sexes. A substantial number of DEGs play roles in synaptic signaling and neuroplasticity. Chromatin immunoprecipitation revealed enrichment of H3 acetylation, a transcriptionally activating chromatin mark. Although broadly similar, some differences were revealed in the gene ontology networks enriched in females and males. Our results cohere with findings from previous studies based on a priori gene selection. Our results also reveal novel genes and molecular pathways that are upregulated by repeated morphine exposure, with some common to males and females and others that are sex-specific.
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影响因子：
4.2
作者：
Becker, Jill B.;McClellan, Michele L.;Reed, Beth Glover
通讯作者：
Reed, Beth Glover
影响因子：
4.2
作者：
Barks, Amanda;Fretham, Stephanie J. B.;Tran, Phu, V
通讯作者：
Tran, Phu, V
影响因子：
4
作者：
Haghparast, Abbas;Fatahi, Zahra;Khodagholi, Fariba
通讯作者：
Khodagholi, Fariba
影响因子：
5.3
作者：
Doyle, Hillary H.;Eidson, Lori N.;Murphy, Anne Z.
通讯作者：
Murphy, Anne Z.
影响因子：
7.6
作者：
Ferrer-Alcón, M;La Harpe, R;García-Sevilla, JA
通讯作者：
García-Sevilla, JA