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感染冠状病毒的小鼠中枢神经系统和膀胱的差异转录组变化。

Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus.

机构信息

Division of Urology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America.

出版信息

PLoS One. 2022 Dec 9;17(12):e0278918. doi: 10.1371/journal.pone.0278918. eCollection 2022.

Abstract

Multiple sclerosis (MS) often leads to the development of neurogenic lower urinary tract symptoms (LUTS). We previously characterized neurogenic bladder dysfunction in a mouse model of MS induced by a coronavirus, mouse hepatitis virus (MHV). The aim of the study was to identify genes and pathways linking neuroinflammation in the central nervous system with urinary bladder (UB) dysfunction to enhance our understanding of the mechanisms underlying LUTS in demyelinating diseases. Adult C57BL/6 male mice (N = 12) received either an intracranial injection of MHV (coronavirus-induced encephalomyelitis, CIE group), or sterile saline (control group). Spinal cord (SC) and urinary bladders (UB) were collected from CIE mice at 1 wk and 4 wks, followed by RNA isolation and NanoString nCounter Neuroinflammation assay. Transcriptome analysis of SC identified a significantly changed expression of >150 genes in CIE mice known to regulate astrocyte, microglia and oligodendrocyte functions, neuroinflammation and immune responses. Two genes were significantly upregulated (Ttr and Ms4a4a), and two were downregulated (Asb2 and Myct1) only in the UB of CIE mice. Siglec1 and Zbp1 were the only genes significantly upregulated in both tissues, suggesting a common transcriptomic link between neuroinflammation in the CNS and neurogenic changes in the UB of CIE mice.

摘要

多发性硬化症(MS)常导致神经源性下尿路症状(LUTS)的发展。我们之前在冠状病毒,鼠肝炎病毒(MHV)诱导的 MS 小鼠模型中描述了神经性膀胱功能障碍。本研究的目的是确定将中枢神经系统中的神经炎症与膀胱(UB)功能障碍联系起来的基因和途径,以增强我们对脱髓鞘疾病中 LUTS 机制的理解。成年 C57BL/6 雄性小鼠(N = 12)接受脑内 MHV 注射(冠状病毒诱导的脑脊髓炎,CIE 组)或无菌盐水(对照组)。在 1 周和 4 周时从 CIE 小鼠中收集脊髓(SC)和膀胱(UB),随后进行 RNA 分离和 NanoString nCounter 神经炎症测定。SC 的转录组分析确定了 150 多个在 CIE 小鼠中表达明显改变的基因,这些基因已知可调节星形胶质细胞、小胶质细胞和少突胶质细胞功能、神经炎症和免疫反应。在 CIE 小鼠的 UB 中,有两个基因(Ttr 和 Ms4a4a)显著上调,有两个基因(Asb2 和 Myct1)下调。只有 Siglec1 和 Zbp1 在两种组织中均显著上调,这表明 CNS 中的神经炎症和 CIE 小鼠 UB 中的神经源性变化之间存在共同的转录组联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c44b/9733897/5d67b778e3ec/pone.0278918.g001.jpg

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