Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation
Dexmedetomidine alleviates host ADHD-like behaviors by reshaping the gut microbiota and reducing gut-brain inflammation
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DOI：
10.1016/j.psychres.2023.115172
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发表时间：
2023-03-21
影响因子：
11.3
通讯作者：
Li，Yan
中科院分区：
文献类型：
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作者：
Xu，Xiangzhao;Zhuo，Lixia;Li，Yan
注意力缺陷多动障碍（ADHD）是影响儿童甚至持续到成年的最常见的精神疾病之一。右美托咪定（DEX）是一种短期镇静剂，可选择性激活α2肾上腺素受体。ADHD患者使用α2-肾上腺素能受体激动剂治疗越来越普遍。然而，DEX治疗ADHD的治疗潜力尚不清楚。在这里，我们评估了DEX对自发性高血压大鼠（SHR）ADHD样行为的影响，SHR是一种广泛使用的ADHD动物模型。DEX治疗改善了SHR的多动和空间工作记忆缺陷，并使θ脑电图（EEG）节律正常化。我们还发现，DEX治疗改变了肠道微生物群组成，并促进了与SHR抗炎作用相关的有益肠道细菌属的富集。DEX给药后，肠道病理评分和通透性以及肠道和脑中观察到的炎症水平显著改善。此外，从DEX治疗的SHR移植粪便微生物群产生的效果模拟DEX给药的治疗效果。因此，DEX是一种很有前途的ADHD治疗方法，它通过重塑肠道微生物群的组成并减少肠道和大脑的炎症来发挥作用。
Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders that affects children and even continues into adulthood. Dexmedetomidine (DEX), a short-term sedative, can selectively activate the α2-adrenoceptor. Treatment with α2-adrenergic agonists in patients with ADHD is becoming increasingly common. However, the therapeutic potential of DEX for the treatment of ADHD is unknown. Here, we evaluated the effect of DEX on ADHD-like behavior in spontaneously hypertensive rats (SHRs), a widely used animal model of ADHD. DEX treatment ameliorated hyperactivity and spatial working memory deficits and normalized θ electroencephalogram (EEG) rhythms in SHRs. We also found that DEX treatment altered the gut microbiota composition and promoted the enrichment of beneficial gut bacterial genera associated with anti-inflammatory effects in SHRs. The gut pathological scores and permeability and the level of inflammation observed in the gut and brain were remarkably improved after DEX administration. Moreover, transplantation of fecal microbiota from DEX-treated SHRs produced effects that mimicked the therapeutic effects of DEX administration. Therefore, DEX is a promising treatment for ADHD that functions by reshaping the composition of the gut microbiota and reducing inflammation in the gut and brain.