Association between inflammation, reward processing, and ibuprofen-induced increases of miR-23b in astrocyte-enriched extracellular vesicles: A randomized, placebo-controlled, double-blind, exploratory trial in healthy individuals.
Association between inflammation, reward processing, and ibuprofen-induced increases of miR-23b in astrocyte-enriched extracellular vesicles: A randomized, placebo-controlled, double-blind, exploratory trial in healthy individuals.
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DOI：
10.1016/j.bbih.2022.100582
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发表时间：
2023-02
期刊：
影响因子：
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中科院分区：
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伊莱克斯是一种非甾体类抗炎药，可调节炎症，但也可能对大脑健康具有神经保护作用，但人们对此知之甚少。富含星形胶质细胞的细胞外囊泡（AEEV）促进细胞间的通讯，并通过微核糖核酸（miRNA）调节炎症和代谢。奖励相关的加工和炎症功能障碍已被认为是情绪障碍患者的重要病理生理途径。本研究检查了抗炎剂诱导的AEEV货物的变化是否导致与奖励相关处理相关的炎症调节。来自健康志愿者的双盲，随机，重复测量研究的数据被用来检查AEEV miRNAs对奖励相关处理过程中大脑激活的影响。在三次单独的访问中，健康参与者（N = 20）接受了安慰剂，200 mg或600 mg布洛芬的单次剂量，在功能性磁共振成像期间完成了货币激励延迟任务，并提供了用于细胞因子和AEEV收集的血液样本。AEEV miRNA含量分析显示，布洛芬剂量依赖性地增加AEEV miR-23 b-3 p表达，600 mg给药后的增加幅度大于安慰剂。接受600 mg且显示最高miR-23 B-3 p表达的个体还显示（a）最低血清肿瘤坏死因子（TNF）和白介素-17 A（IL-17 A）浓度;并且在奖励预期期间具有（B）最高纹状体脑激活。这些结果支持布洛芬改变AEEV中miRNA组成的假设。这开启了AEEV货物可用于调节对心理健康重要的大脑过程的可能性。急性给予600 mg伊莱克斯导致更高的AEEV miR-23 b表达。较高的AEEV miR-23 b与较低的血清TNF和IL-17 A相关。更高的AEEV miR-23 b与更大的纹状体奖励预期信号相关。
Ibuprofen, a non-steroidal, anti-inflammatory drug, modulates inflammation but may also have neuroprotective effects on brain health that are poorly understood. Astrocyte-enriched extracellular vesicles (AEEVs) facilitate cell-to-cell communication and – among other functions - regulate inflammation and metabolism via microribonucleic acids (miRNAs). Dysfunctions in reward-related processing and inflammation have been proposed to be critical pathophysiological pathways in individuals with mood disorders. This investigation examined whether changes in AEEV cargo induced by an anti-inflammatory agent results in inflammatory modulation that is associated with reward-related processing. Data from a double-blind, randomized, repeated-measures study in healthy volunteers were used to examine the effects of AEEV miRNAs on brain activation during reward-related processing. In three separate visits, healthy participants (N = 20) received a single dose of either placebo, 200 mg, or 600 mg of ibuprofen, completed the monetary incentive delay task during functional magnetic resonance imaging, and provided a blood sample for cytokine and AEEV collection. AEEV miRNA content profiling showed that ibuprofen dose-dependently increased AEEV miR-23b-3p expression with greater increase following the 600 mg administration than placebo. Those individuals who received 600 mg and showed the highest miR-23b-3p expression also showed the (a) lowest serum tumor necrosis factor (TNF) and interleukin-17A (IL-17A) concentrations; and had the (b) highest striatal brain activation during reward anticipation. These results support the hypothesis that ibuprofen alters the composition of miRNAs in AEEVs. This opens the possibility that AEEV cargo could be used to modulate brain processes that are important for mental health. Acute administration of 600 mg Ibuprofen resulted in higher AEEV miR-23b expression. Higher AEEV miR-23b was associated with lower serum TNF and IL-17A. Higher AEEV miR-23b was associated with greater striatal reward anticipation signaling.
DOI：
10.1016/j.bbi.2021.05.023
发表时间：
2021-08
期刊：
Brain, behavior, and immunity
影响因子：
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作者：
Cosgrove KT;Kuplicki R;Savitz J;Burrows K;Simmons WK;Khalsa SS;Teague TK;Aupperle RL;Paulus MP
通讯作者：
Paulus MP
布洛芬对脑的影响：一项随机，安慰剂对照的剂量反应探索性研究。
DOI：
10.1016/j.bpsc.2018.05.002
发表时间：
2018-10
期刊：
Biological psychiatry. Cognitive neuroscience and neuroimaging
影响因子：
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作者：
Le TT;Kuplicki R;Yeh HW;Aupperle RL;Khalsa SS;Simmons WK;Paulus MP
通讯作者：
Paulus MP