Cargando…
Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice
Microglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific kn...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472527/ https://www.ncbi.nlm.nih.gov/pubmed/36878712 http://dx.doi.org/10.1111/cpr.13439 |
_version_ | 1785100095515000832 |
---|---|
author | Liu, Cong Gao, Xing Shi, Ruo‐Xi Wang, Ying‐Ying He, Xuan‐Cheng Du, Hong‐Zhen Hu, Baoyang Jiao, Jianwei Liu, Chang‐Mei Teng, Zhao‐Qian |
author_facet | Liu, Cong Gao, Xing Shi, Ruo‐Xi Wang, Ying‐Ying He, Xuan‐Cheng Du, Hong‐Zhen Hu, Baoyang Jiao, Jianwei Liu, Chang‐Mei Teng, Zhao‐Qian |
author_sort | Liu, Cong |
collection | PubMed |
description | Microglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific knockout of Tgm2 in microglia was generated. Immunohistochemistry, Western blot and qRT‐PCR assays were performed to evaluate the expression levels of TGM2, PSD‐95 and CD68. Confocal imaging, immunofluorescence staining and behavioural analyses were conducted to identify phenotypes of microglial TGM2 deficiency. Finally, RNA sequencing, qRT‐PCR and co‐culture of neurons and microglia were used to explore the potential mechanisms. Deletion of microglial Tgm2 causes impaired synaptic pruning, reduced anxiety and increased cognitive deficits in mice. At the molecular level, the phagocytic genes, such as Cq1a, C1qb and Tim4, are significantly down‐regulated in TGM2‐deficient microglia. This study elucidates a novel role of microglial TGM2 in regulating synaptic remodelling and cognitive function, indicating that microglia Tgm2 is essential for proper neural development. |
format | Online Article Text |
id | pubmed-10472527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104725272023-09-02 Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice Liu, Cong Gao, Xing Shi, Ruo‐Xi Wang, Ying‐Ying He, Xuan‐Cheng Du, Hong‐Zhen Hu, Baoyang Jiao, Jianwei Liu, Chang‐Mei Teng, Zhao‐Qian Cell Prolif Original Articles Microglia are the primary source of transglutaminase 2 (TGM2) in the brain; however, the roles of microglial TGM2 in neural development and disease are still not well known. The aim of this study is to elucidate the role and mechanisms of microglial TGM2 in the brain. A mouse line with a specific knockout of Tgm2 in microglia was generated. Immunohistochemistry, Western blot and qRT‐PCR assays were performed to evaluate the expression levels of TGM2, PSD‐95 and CD68. Confocal imaging, immunofluorescence staining and behavioural analyses were conducted to identify phenotypes of microglial TGM2 deficiency. Finally, RNA sequencing, qRT‐PCR and co‐culture of neurons and microglia were used to explore the potential mechanisms. Deletion of microglial Tgm2 causes impaired synaptic pruning, reduced anxiety and increased cognitive deficits in mice. At the molecular level, the phagocytic genes, such as Cq1a, C1qb and Tim4, are significantly down‐regulated in TGM2‐deficient microglia. This study elucidates a novel role of microglial TGM2 in regulating synaptic remodelling and cognitive function, indicating that microglia Tgm2 is essential for proper neural development. John Wiley and Sons Inc. 2023-03-06 /pmc/articles/PMC10472527/ /pubmed/36878712 http://dx.doi.org/10.1111/cpr.13439 Text en © 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Liu, Cong Gao, Xing Shi, Ruo‐Xi Wang, Ying‐Ying He, Xuan‐Cheng Du, Hong‐Zhen Hu, Baoyang Jiao, Jianwei Liu, Chang‐Mei Teng, Zhao‐Qian Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
title | Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
title_full | Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
title_fullStr | Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
title_full_unstemmed | Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
title_short | Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
title_sort | microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472527/ https://www.ncbi.nlm.nih.gov/pubmed/36878712 http://dx.doi.org/10.1111/cpr.13439 |
work_keys_str_mv | AT liucong microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT gaoxing microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT shiruoxi microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT wangyingying microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT hexuancheng microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT duhongzhen microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT hubaoyang microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT jiaojianwei microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT liuchangmei microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice AT tengzhaoqian microglialtransglutaminase2deficiencycausesimpairedsynapticremodellingandcognitivedeficitsinmice |