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

作者：Yunmeng Bai, Zhuhe Liu, Tinglin Qian, Peng Yu, Huan Ma, Hong Hu, Guangqing Cheng, Haixia Wen, Lulin Xie, Dong Zheng, Qingshan Geng, Jigang Wang, Honghao Wang · 发表于：Brain Pathology · 年份：2023 · DOI：10.1111/bpa.13156 · 被引用次数：11 · 研究领域：RNA regulation and disease、interferon and immune responses、Autoimmune Neurological Disorders and Treatments

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.