Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia.
Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia.
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DOI：
10.3390/ijms24098091
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发表时间：
2023-04-30
影响因子：
5.6
通讯作者：
Zhu, Weifei
中科院分区：
文献类型：
--
作者：
Kaur, Navdeep;LaForce, Geneva;Mallela, Deepthi P.;Saha, Prasenjit Prasad;Buffa, Jennifer;Li, Xinmin S. S.;Sangwan, Naseer;Rothenberg, Kasia;Zhu, Weifei
中风是认知障碍和痴呆的第二大常见原因。血管性痴呆（VaD）是中风后的一种认知障碍，很常见，严重影响生活质量。我们最近通过肠道微生物移植研究证明，肠道微生物依赖性三甲胺-N-氧化物（TMAO）途径影响卒中严重程度，包括梗死面积和长期认知结果。然而，微生物群在VaD中作用的分子机制尚未深入探讨。为了解决这个问题，我们进行了一个全面的RNA测序分析，以确定差异表达（DE）基因在缺血性大脑皮层的小鼠脑中风前和中风后第1天和第3天。在中风前和中风后第1天和第3天分别鉴定了总共4016、3752和7861个DE基因。京都基因和基因组百科全书（KEGG）富集分析表明多种疾病中的神经变性途径、趋化因子信号传导、钙信号传导和IL-17信号传导是关键富集途径。炎症反应基因白细胞介素-1 β（IL-1β）、趋化因子（C-X-C基序趋化因子配体10（Cxcl 10）、趋化因子配体2（Ccl 2））和免疫系统基因（S100钙结合蛋白8（S100 a8）、脂质运载蛋白-2（Lcn 2））是最显著上调的基因。下丘脑泌素神经肽前体（Hcrt）（一种神经肽）和转录因子如神经元PAS结构域蛋白4（Npas 4）、加塔结合蛋白3（Gata 3）和配对盒7（Pax 7）是最显著下调的基因。总之，我们的研究结果表明，在我们的临床前中风模型中，较高的血浆TMAO水平诱导缺血性脑组织中的差异mRNA表达谱，并且预测的途径为调节TMAO增强的脑中神经炎症反应提供了分子基础。
Stroke is the second most common cause of cognitive impairment and dementia. Vascular dementia (VaD), a cognitive impairment following a stroke, is common and significantly impacts the quality of life. We recently demonstrated via gut microbe transplant studies that the gut microbe-dependent trimethylamine-N-oxide (TMAO) pathway impacts stroke severity, both infarct size and long-term cognitive outcomes. However, the molecular mechanisms that underly the role of the microbiome in VaD have not been explored in depth. To address this issue, we performed a comprehensive RNA-sequencing analysis to identify differentially expressed (DE) genes in the ischemic cerebral cortex of mouse brains at pre-stroke and post-stroke day 1 and day 3. A total of 4016, 3752 and 7861 DE genes were identified at pre-stroke and post-stroke day 1 and day 3, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated pathways of neurodegeneration in multiple diseases, chemokine signaling, calcium signaling, and IL-17 signaling as the key enriched pathways. Inflammatory response genes interleukin-1 beta (Il-1β), chemokines (C–X–C motif chemokine ligand 10 (Cxcl10), chemokine ligand 2 (Ccl2)), and immune system genes (S100 calcium binding protein 8 (S100a8), lipocalin-2 (Lcn2)) were among the most significantly upregulated genes. Hypocretin neuropeptide precursor (Hcrt), a neuropeptide, and transcription factors such as neuronal PAS domain protein 4 (Npas4), GATA binding protein 3 (Gata3), and paired box 7 (Pax7) were among the most significantly downregulated genes. In conclusion, our results indicate that higher plasma TMAO levels induce differential mRNA expression profiles in the ischemic brain tissue in our pre-clinical stroke model, and the predicted pathways provide the molecular basis for regulating the TMAO-enhanced neuroinflammatory response in the brain.
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影响因子：
8.3
作者：
Corraini, Priscila;Henderson, Victor W.;Sorensen, Henrik T.
通讯作者：
Sorensen, Henrik T.
人类肠道微生物群：与痴呆症发展的联系
影响因子：
21.1
作者：
Alkasir R;Li J;Li X;Jin M;Zhu B
通讯作者：
Zhu B
影响因子：
15.1
作者：
Connell, Emily;Le Gall, Gwenaelle;Pontifex, Matthew G.;Sami, Saber;Cryan, John F.;Clarke, Gerard;Mueller, Michael;Vauzour, David
通讯作者：
Vauzour, David
影响因子：
4.6
作者：
Harach T;Marungruang N;Duthilleul N;Cheatham V;Mc Coy KD;Frisoni G;Neher JJ;Fåk F;Jucker M;Lasser T;Bolmont T
通讯作者：
Bolmont T
影响因子：
7.1
作者：
Holtman IR;Raj DD;Miller JA;Schaafsma W;Yin Z;Brouwer N;Wes PD;Möller T;Orre M;Kamphuis W;Hol EM;Boddeke EW;Eggen BJ
通讯作者：
Eggen BJ