Sleep dysfunction and gut dysbiosis related amino acids metabolism disorders in cynomolgus monkeys after middle cerebral artery occlusion

IF 4.6 2区 医学 Q1 NEUROSCIENCES Experimental Neurology Pub Date : 2024-09-24 DOI:10.1016/j.expneurol.2024.114970
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Abstract

Introduction

This study aimed to explore the characteristics of post-stroke sleep dysfunction and verify their association with gut dysbiosis and the related amino acid metabolism disorders. This was achieved by using fecal microbiota transplantation (FMT) in a non-human primate stroke model.

Methods

Twenty adult male cynomolgus monkeys were divided into the sham (n = 4), middle cerebral artery occlusion (MCAO, n = 5), MCAO + FMT (n = 3), and donor (n = 8) groups. The MCAO+FMT group received FMT at post-MCAO week 4. Sleep parameters, gut microbiota, gamma-aminobutyric acid (GABA), and glutamine (Gln) in the cerebrospinal fluid (CSF) were measured at baseline and postoperative weeks 4, 8, and 12.

Results

At postoperative weeks 4, 8, and 12, the MCAO group showed decreased sleep efficiency, measured as the percentage of sleep during the whole night (82.3 ± 3.2 % vs 91.3 ± 2.5 %, 79.0 ± 3.75 % vs 90.8 ± 3.2 %, and 69.5 ± 4.8 % vs 90.5 ± 2.7 %; all P < 0.05), lower relative abundance of Lactobacillus (all P < 0.05), and reduced GABA concentrations in the CSF (317.3 ± 30.6 nmol/L vs 437.7 ± 25.6 nmol/L, 303.1 ± 48.9 nmol/L vs 4 40.9 ± 37.8 nmol/L, and 337.9 ± 49.4 nmol/L vs 457.4 ± 39.2 nmol/L; all P < 0.05) compared with the sham group. Sleep efficiency at post-FMT weeks 4 and 8 (84.7 ± 1.1 % vs 79.0 ± 3.75 %, and 84.1 ± 2.0 % vs 69.5 ± 4.8 %; both P < 0.05) and GABA concentration in the CSF at post-FMT week 4 (403.1 ± 25.4 nmol/L vs 303.1 ± 48.9 nmol/L, P < 0.05) was higher in the MCAO+FMT group than in the MCAO group.

Conclusions

Post-stroke sleep dysfunction in monkeys is characterized by impaired sleep coherence, associated with decreased levels of probiotics such as Lactobacillus, GABA, and Gln in the CSF and can be ameliorated using FMT.
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大脑中动脉闭塞后猴的睡眠功能障碍和肠道菌群失调导致的氨基酸代谢紊乱
简介本研究旨在探索中风后睡眠功能障碍的特征,并验证其与肠道菌群失调及相关氨基酸代谢紊乱的关系。方法:在非人灵长类中风模型中使用粪便微生物群移植(FMT):方法:20 只成年雄性眼镜猴被分为假组(n = 4)、大脑中动脉闭塞组(MCAO,n = 5)、MCAO + FMT 组(n = 3)和供体组(n = 8)。MCAO+FMT组在MCAO后第4周接受FMT治疗。在基线和术后第 4、8 和 12 周测量睡眠参数、肠道微生物群、γ-氨基丁酸(GABA)和脑脊液(CSF)中的谷氨酰胺(Gln):结果:在术后第 4、8 和 12 周,MCAO 组的睡眠效率下降,以整夜睡眠的百分比来衡量(82.3 ± 3.2 % vs 91.3 ± 2.5 %、79.0 ± 3.75 % vs 90.8 ± 3.2 % 和 69.5 ± 4.8 % vs 90.5 ± 2.7 %;均为 P 结论:MCAO 组的睡眠效率高于 MCAO 组(P<0.05):中风后猴子睡眠功能障碍的特点是睡眠连贯性受损,与脑脊液中益生菌(如乳酸杆菌、GABA和Gln)水平下降有关,可通过FMT改善。
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来源期刊
Experimental Neurology
Experimental Neurology 医学-神经科学
CiteScore
10.10
自引率
3.80%
发文量
258
审稿时长
42 days
期刊介绍: Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.
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