Neuronally-enriched exosomal microRNA-27b mediates acute effects of ibuprofen on reward-related brain activity in healthy adults: a randomized, placebo-controlled, double-blind trial

富含神经元的外泌体 microRNA-27b 介导布洛芬对健康成人奖赏相关大脑活动的急性影响:一项随机、安慰剂对照、双盲试验

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作者:Kaiping Burrows, Leandra K Figueroa-Hall, Rayus Kuplicki, Jennifer L Stewart, Ahlam M Alarbi, Rajagopal Ramesh, Jonathan B Savitz, T Kent Teague, Victoria B Risbrough, Martin P Paulus

Abstract

This double-blind, randomized, within-subjects design evaluated whether acute administration of an anti-inflammatory drug modulates neuron-specific, inflammation-modulating microRNAs linked to macroscopic changes in reward processing. Twenty healthy subjects (10 females, 10 males) underwent a functional magnetic resonance imaging scan while performing a monetary incentive delay (MID) task and provided blood samples after administration of placebo, 200 mg, or 600 mg of ibuprofen. Neuronally-enriched exosomal microRNAs were extracted from serum and sequenced. Results showed that: (1) 600 mg of ibuprofen exhibited higher miR-27b-3p, miR-320b, miR-23b and miR-203a-3p expression than placebo; (2) higher mir-27b-3p was associated with lower insula activation during MID loss anticipation; and (3) there was an inverse relationship between miR-27b-3p and MID gain anticipation in bilateral putamen during placebo, a pattern attenuated by both 200 mg and 600 mg of ibuprofen. These findings are consistent with the hypothesis that miR-27b could be an important messaging molecule that is associated with regulating the processing of positive or negative valenced information.

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