Cerebellar connectome alterations and associated genetic signatures in multiple sclerosis and neuromyelitis optica spectrum disorder

作者全名："Yang, Yuping; Li, Junle; Li, Ting; Li, Zhen; Zhuo, Zhizheng; Han, Xuemei; Duan, Yunyun; Cao, Guanmei; Zheng, Fenglian; Tian, Decai; Wang, Xinli; Zhang, Xinghu; Li, Kuncheng; Zhou, Fuqing; Huang, Muhua; Li, Yuxin; Li, Haiqing; Li, Yongmei; Zeng, Chun; Zhang, Ningnannan; Sun, Jie; Yu, Chunshui; Shi, Fudong; Asgher, Umer; Muhlert, Nils; Liu, Yaou; Wang, Jinhui"

作者地址："[Yang, Yuping; Li, Junle; Li, Ting; Li, Zhen; Wang, Jinhui] South China Normal Univ, Inst Brain Res & Rehabil, Zhongshan Ave West 55, Guangzhou 510631, Peoples R China; [Yang, Yuping; Muhlert, Nils] Univ Manchester, Fac Biol Med & Hlth, Sch Hlth Sci, Oxford Rd, Manchester M13 9PT, England; [Zhuo, Zhizheng; Duan, Yunyun; Cao, Guanmei; Zheng, Fenglian; Liu, Yaou] Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China; [Han, Xuemei] Jilin Univ, China Japan Union Hosp, Dept Neurol, Changchun 130031, Jilin, Peoples R China; [Tian, Decai; Zhang, Xinghu; Shi, Fudong] Capital Med Univ, Beijing Tiantan Hosp, Ctr Neurol, Beijing 100070, Peoples R China; [Tian, Decai; Shi, Fudong] China Natl Clin Res Ctr Neurol Dis, Beijing 100070, Peoples R China; [Wang, Xinli; Shi, Fudong] Tianjin Med Univ, Gen Hosp, Tianjin Neurol Inst, Dept Neurol, Tianjin 300052, Peoples R China; [Li, Kuncheng] Capital Med Univ, Xuanwu Hosp, Dept Radiol, Beijing 100053, Peoples R China; [Zhou, Fuqing; Huang, Muhua] Nanchang Univ, Affiliated Hosp 1, Dept Radiol, Nanchang 330006, Jiangxi, Peoples R China; [Zhou, Fuqing; Huang, Muhua] Jiangxi Prov Med Imaging Res Inst, Neuroimaging Lab, Nanchang 330006, Jiangxi, Peoples R China; [Li, Yuxin; Li, Haiqing] Fudan Univ, Huashan Hosp, Dept Radiol, Shanghai 200040, Peoples R China; [Li, Yongmei; Zeng, Chun] Chongqing Med Univ, Affiliated Hosp 1, Dept Radiol, Chongqing 400016, Peoples R China; [Zhang, Ningnannan; Sun, Jie; Yu, Chunshui] Tianjin Med Univ, Gen Hosp, Dept Radiol, Tianjin 300052, Peoples R China; [Zhang, Ningnannan; Sun, Jie; Yu, Chunshui] Tianjin Med Univ, Gen Hosp, Tianjin Key Lab Funct Imaging, Tianjin 300052, Peoples R China; [Asgher, Umer] Natl Univ Sci & Technol NUST, Sch Mech & Mfg Engn SMME, Islamabad, Pakistan; [Wang, Jinhui] Minist Educ, Key Lab Brain Cognit & Educ Sci, Guangzhou 510631, Peoples R China; [Wang, Jinhui] South China Normal Univ, Guangdong Key Lab Mental Hlth & Cognit Sci, Guangzhou 510631, Peoples R China; [Wang, Jinhui] South China Normal Univ, Ctr Studies Psychol Applicat, Guangzhou 510631, Peoples R China"

通信作者："Wang, JH (通讯作者)，South China Normal Univ, Inst Brain Res & Rehabil, Zhongshan Ave West 55, Guangzhou 510631, Peoples R China.; Liu, YU (通讯作者)，Capital Med Univ, Beijing Tiantan Hosp, Dept Radiol, 119,West Southern 4th Ring Rd, Beijing 100070, Peoples R China.; Wang, JH (通讯作者)，Minist Educ, Key Lab Brain Cognit & Educ Sci, Guangzhou 510631, Peoples R China.; Wang, JH (通讯作者)，South China Normal Univ, Guangdong Key Lab Mental Hlth & Cognit Sci, Guangzhou 510631, Peoples R China.; Wang, JH (通讯作者)，South China Normal Univ, Ctr Studies Psychol Applicat, Guangzhou 510631, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000996034900003

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Multiple sclerosis; Neuromyelitis optica spectrum disorder; Cerebellum; Structural and functional MRI; Genetic correlates

摘要："BackgroundThe cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown.MethodsCombining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles.ResultsDespite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases.ConclusionsWe demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases."

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