PMID- 36942475
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20230703
IS  - 1750-3639 (Electronic)
IS  - 1015-6305 (Print)
IS  - 1015-6305 (Linking)
VI  - 33
IP  - 4
DP  - 2023 Jul
TI  - Single-nucleus RNA sequencing unveils critical regulators in various hippocampal 
      neurons for anti-N-methyl-D-aspartate receptor encephalitis.
PG  - e13156
LID - 10.1111/bpa.13156 [doi]
LID - e13156
AB  - 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.
CI  - (c) 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf 
      of International Society of Neuropathology.
FAU - Bai, Yunmeng
AU  - Bai Y
AD  - Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen 
      People's Hospital, the First Affiliated Hospital, School of Medicine, Southern 
      University of Science and Technology, Shenzhen, China.
FAU - Liu, Zhuhe
AU  - Liu Z
AD  - Department of Neurology, Guangzhou First People's Hospital, School of Medicine, 
      Southern China University of Technology, Guangzhou, China.
FAU - Qian, Tinglin
AU  - Qian T
AD  - School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 
      China.
FAU - Peng, Yu
AU  - Peng Y
AD  - Department of Neurology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, China.
FAU - Ma, Huan
AU  - Ma H
AD  - Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 
      Guangzhou, China.
FAU - Hu, Hong
AU  - Hu H
AD  - Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen 
      People's Hospital, the First Affiliated Hospital, School of Medicine, Southern 
      University of Science and Technology, Shenzhen, China.
FAU - Cheng, Guangqing
AU  - Cheng G
AD  - Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen 
      People's Hospital, the First Affiliated Hospital, School of Medicine, Southern 
      University of Science and Technology, Shenzhen, China.
FAU - Wen, Haixia
AU  - Wen H
AD  - Department of Neurology, Guangzhou First People's Hospital, School of Medicine, 
      Southern China University of Technology, Guangzhou, China.
FAU - Xie, Lulin
AU  - Xie L
AD  - Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen 
      People's Hospital, the First Affiliated Hospital, School of Medicine, Southern 
      University of Science and Technology, Shenzhen, China.
FAU - Zheng, Dong
AU  - Zheng D
AD  - Department of Neurology, The Affiliated Brain Hospital of Guangzhou Medical 
      University, Guangzhou, China.
FAU - Geng, Qingshan
AU  - Geng Q
AD  - Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen 
      People's Hospital, the First Affiliated Hospital, School of Medicine, Southern 
      University of Science and Technology, Shenzhen, China.
FAU - Wang, Jigang
AU  - Wang J
AD  - Department of Nephrology, Shenzhen Key Laboratory of Kidney Diseases, Shenzhen 
      People's Hospital, the First Affiliated Hospital, School of Medicine, Southern 
      University of Science and Technology, Shenzhen, China.
FAU - Wang, Honghao
AU  - Wang H
AUID- ORCID: 0000-0002-1215-6219
AD  - Department of Neurology, Guangzhou First People's Hospital, School of Medicine, 
      Southern China University of Technology, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230321
PL  - Switzerland
TA  - Brain Pathol
JT  - Brain pathology (Zurich, Switzerland)
JID - 9216781
RN  - 0 (Autoantibodies)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Anti-N-Methyl-D-Aspartate Receptor Encephalitis/genetics/metabolism/pathology
MH  - Hippocampus/pathology
MH  - Neurons/pathology
MH  - Autoantibodies
MH  - Sequence Analysis, RNA
PMC - PMC10307523
OTO - NOTNLM
OT  - anti-N-methyl-D-aspartate receptor encephalitis
OT  - hippocampus
OT  - neuronal types
OT  - single-nucleus RNA sequencing
COIS- The authors declare no conflicts of interest.
EDAT- 2023/03/22 06:00
MHDA- 2023/06/30 06:42
PMCR- 2023/03/21
CRDT- 2023/03/21 03:53
PHST- 2022/06/27 00:00 [received]
PHST- 2023/02/28 00:00 [accepted]
PHST- 2023/06/30 06:42 [medline]
PHST- 2023/03/22 06:00 [pubmed]
PHST- 2023/03/21 03:53 [entrez]
PHST- 2023/03/21 00:00 [pmc-release]
AID - BPA13156 [pii]
AID - 10.1111/bpa.13156 [doi]
PST - ppublish
SO  - Brain Pathol. 2023 Jul;33(4):e13156. doi: 10.1111/bpa.13156. Epub 2023 Mar 21.