Single-nucleus RNA sequencing unveils critical regulators in various hippocampal neurons for anti-N-methyl-D-aspartate receptor encephalitis

Bai, Yunmeng1; Liu, Zhuhe2; Qian, Tinglin3; Peng, Yu4; Ma, Huan5; Hu, Hong1; Cheng, Guangqing1; Wen, Haixia2; Xie, Lulin1; Zheng, Dong6; Geng, Qingshan1,7,8; Wang, Jigang1,7,8; Wang, Honghao2,9

2023-03-01

10.1111/bpa.13156

BRAIN PATHOLOGY   Impact Factor & Quartile

1015-6305

1750-3639

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a neuropsychiatric disease with variable clinical manifestations caused by NMDAR autoantibody. The underlying molecular underpinnings of this disease are rarely characterized on a genomic scale. Anti-NMDAR encephalitis mainly affects the hippocampus, however, its effect on gene expression in hippocampal neurons is unclear at present. Here, we construct the active and passive immunization mouse models of anti-NMDAR encephalitis, and use single-nucleus RNA sequencing to investigate the diverse expression profile of neuronal populations isolated from different hippocampal regions. Dramatic changes in cell proportions and differentially expressed genes were observed in excitatory neurons of the dentate gyrus (DG) subregion. In addition, we found that ATP metabolism and biosynthetic regulators related genes in excitatory neurons of DG subregion were significantly affected. Kcnq1ot1 in inhibitory neurons and Meg3 in interneurons also changed. Notably, the latter two molecules exhibited opposite changes in different models. Therefore, the above genes were used as potential targets for further research on the pathological process of anti-NMDAR encephalitis. These data involve various hippocampal neurons, which delineate a framework for understanding the hippocampal neuronal circuit and the potential molecular mechanisms of anti-NMDAR encephalitis.

anti-N-methyl-D-aspartate receptor encephalitis hippocampus neuronal types single-nucleus RNA sequencing

SCI

English

First ; Corresponding

National Natural Science Foundation of China["81901239","82171354"]

Neurosciences & Neurology ; Pathology

Clinical Neurology ; Neurosciences ; Pathology

WOS:000950771200001

WILEY

NEUROSCIENCE & BEHAVIOR

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Sch Med,Dept Nephrol,Shenzhen Key Lab Kidney Dis, Shenzhen, Peoples R China
2.Southern China Univ Technol, Guangzhou First Peoples Hosp, Sch Med, Dept Neurol, Guangzhou, Peoples R China
3.Southern Med Univ, Sch Tradit Chinese Med, Guangzhou, Peoples R China
4.Southern Med Univ, Nanfang Hosp, Dept Neurol, Guangzhou, Peoples R China
5.Guangdong Acad Med Sci, Guangdong Cardiovasc Inst, Guangzhou, Peoples R China
6.Guangzhou Med Univ, Affiliated Brain Hosp, Dept Neurol, Guangzhou, Peoples R China
7.Southern Univ Sci & Technol, Dept Nephrol, Shenzhen 518055, Peoples R China
8.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Key Lab Kidney Dis, Shenzhen 518055, Peoples R China
9.Southern China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Neurol, Guangzhou 510180, Peoples R China

Bai, Yunmeng,Liu, Zhuhe,Qian, Tinglin,et al. Single-nucleus RNA sequencing unveils critical regulators in various hippocampal neurons for anti-N-methyl-D-aspartate receptor encephalitis[J]. BRAIN PATHOLOGY,2023.

Bai, Yunmeng.,Liu, Zhuhe.,Qian, Tinglin.,Peng, Yu.,Ma, Huan.,...&Wang, Honghao.(2023).Single-nucleus RNA sequencing unveils critical regulators in various hippocampal neurons for anti-N-methyl-D-aspartate receptor encephalitis.BRAIN PATHOLOGY.

Bai, Yunmeng,et al."Single-nucleus RNA sequencing unveils critical regulators in various hippocampal neurons for anti-N-methyl-D-aspartate receptor encephalitis".BRAIN PATHOLOGY (2023).