Microglial transglutaminase 2 deficiency causes impaired synaptic remodelling and cognitive deficits in mice.
Cell Prolif
; 56(9): e13439, 2023 Sep.
Article
em En
| MEDLINE
| ID: mdl-36878712
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Microglia
/
Proteína 2 Glutamina gama-Glutamiltransferase
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article