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

Differential transcriptomic changes in the central nervous system and urinary bladders of mice infected with a coronavirus.
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DOI:
10.1371/journal.pone.0278918
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发表时间:
2022
期刊:
影响因子:
3.7
通讯作者:
Malykhina, Anna P.
Malykhina, Anna P.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Clarkson, Taylor C.;Iguchi, Nao;Xie, Alison Xiaoqiao;Malykhina, Anna P.

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多发性硬化症(MS)常导致神经源性下尿路症状(LUTS)的发展。我们之前在一种由冠状病毒--小鼠肝炎病毒(MHV)诱导的多发性硬化症小鼠模型中描述了神经源性膀胱功能障碍。本研究的目的是确定中枢神经系统炎症与膀胱功能障碍(UB)之间的基因和途径,以加强我们对LUTS在脱髓鞘疾病中的作用机制的理解。成年C57BL/6雄性小鼠(N=12)接受MHV(冠状病毒诱导的脑脊髓炎,CIE组)或无菌生理盐水(对照组)脑内注射。分别于1wk和4wk取CIE小鼠的脊髓(SC)和膀胱(UB),进行RNA提取和纳米串抗神经炎实验。对SC的转录组分析发现,在CIE小鼠中,>150基因的表达发生了显著变化,已知的基因调控星形胶质细胞、小胶质细胞和少突胶质细胞的功能、神经炎症和免疫反应。两个基因(Ttr和Ms4a4a)显著上调,而两个基因(Asb2和Myct1)仅在CIE小鼠的Ub中表达下调。Siglec1和Zbp1是这两个组织中仅有的显著上调的基因,这表明CIE小鼠中枢神经系统的神经炎症和UB的神经源性变化之间存在共同的转录转录联系。
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.
DOI: 10.1126/scitranslmed.aam7816
发表时间: 2017-12-06
影响因子: 17.1
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Fard MK;van der Meer F;Sánchez P;Cantuti-Castelvetri L;Mandad S;Jäkel S;Fornasiero EF;Schmitt S;Ehrlich M;Starost L;Kuhlmann T;Sergiou C;Schultz V;Wrzos C;Brück W;Urlaub H;Dimou L;Stadelmann C;Simons M
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发表时间: 2010
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