Analysis of Age-Dependent Transcriptomic Changes in Response to Intracerebral Hemorrhage in Mice

作者全名："Li, Xinhui; Yang, Wensong; Shen, Yiqing; Liu, Fangyu; Xiong, Xin; Wu, Qingyuan; Xiao, Zhongsong; Yang, Xun; Dang, Ruozhi; Manaenko, Anatol; Xie, Peng; Li, Qi"

作者地址："[Li, Xinhui; Yang, Wensong; Shen, Yiqing; Liu, Fangyu; Xiao, Zhongsong; Yang, Xun; Dang, Ruozhi; Manaenko, Anatol; Xie, Peng; Li, Qi] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China; [Li, Xinhui; Yang, Wensong; Shen, Yiqing; Liu, Fangyu; Xiao, Zhongsong; Yang, Xun; Dang, Ruozhi; Manaenko, Anatol; Xie, Peng; Li, Qi] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing, Peoples R China; [Xiong, Xin] Chongqing Hosp Tradit Chinese Med, Dept Neurol, Chongqing, Peoples R China; [Wu, Qingyuan] Chongqing Univ Three Gorges Hosp, Dept Neurol, Chongqing, Peoples R China"

通信作者："Xie, P; Li, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China.; Xie, P; Li, Q (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, Chongqing, Peoples R China."

来源：FRONTIERS IN MOLECULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000807208200001

JCR分区：Q2

影响因子：4.8

年份：2022

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：aging; inflammation; intracerebral hemorrhage; type I interferon; transcriptomics; neurological deficit

摘要："Age is a well-known risk factor that is independently associated with poor outcomes after intracerebral hemorrhage (ICH). However, the interrelationship between age and poor outcomes after ICH is not well defined. In this study, we aimed to investigate this relationship based on collagenase-induced ICH mice models. After being assessed neurological deficit 24 h after ICH, mice were euthanized and brain perihematomal tissues were used for RNA-sequencing (RNA-seq). And then the functions of differentially expressed genes (DEGs) identified by RNA-seq were analyzed using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Ingenuity Pathway Analysis (IPA) and protein-protein interaction (PPI) analysis. In addition, we performed real-time quantitative polymerase chain reaction (RT-qPCR) for validation of candidate DEGs. In the behavioral tests, aged mice presented significantly worse neurological function than young mice and greater weight loss than aged sham controls 24 h after ICH. In DEGs analysis, ICH affected the expression of more genes in young mice (2,337 DEGs) compared with aged mice (2,005 DEGs). We found aged mice exhibited increased brain inflammatory responses compared with young animals and ICH induced significant activation of the interferon-beta (IFN-beta) and IFN signaling pathways exclusively in aged mice. Moreover, further analysis demonstrated that ICH resulted in the activation of cytosolic DNA-sensing pathway with the production of downstream molecule type I IFN, and the response to type I IFN was more significant in aged mice than in young mice. In agreement with the results of RNA-seq, RT-qPCR indicated that the expression of candidate genes of cyclic GMP-AMP synthase (cGAS), Z-DNA-binding protein 1 (ZBP1), and IFN-beta was significantly altered in aged mice after ICH. Taken together, our study indicated that compared to young animals, aged mice exhibit increased vulnerability to ICH and that the differences in transcriptional response patterns to ICH between young and aged mice. We believe that these findings will facilitate our understanding of ICH pathology and help to translate the results of preclinical studies into a clinical setting."

基金机构："National Natural Science Foundation of China [82071337]; National Key R&D Program of China [2018YFC1312200, 2018YFC1312203]; Chongqing High-end Young Investigator Project [2019GDRC005]; Science and Technology Innovation Project of ""Chengdu Chongqing Economic Circle"" [KJCXZD2020019]; Excellent Youth Foundation of Chongqing Scientific Committee [cstc2021jcyj-jqX0029]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; National Administration of Traditional Chinese Medicine: 2019 Project of building evidence based practice capacity for TCM [2019XZZX-NB014]"

基金资助正文："This study was supported by grants from National Natural Science Foundation of China (No. 82071337), the National Key R&D Program of China (Nos. 2018YFC1312200 and 2018YFC1312203), Chongqing High-end Young Investigator Project (No. 2019GDRC005), the Science and Technology Innovation Project of ""Chengdu Chongqing Economic Circle"" (No. KJCXZD2020019), the Excellent Youth Foundation of Chongqing Scientific Committee (cstc2021jcyj-jqX0029), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No. 2019PT320002), and the National Administration of Traditional Chinese Medicine: 2019 Project of building evidence based practice capacity for TCM (No. 2019XZZX-NB014)."