Adult microglial TGFß1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice.
Nat Commun
; 15(1): 5306, 2024 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-38906887
ABSTRACT
While TGF-ß signaling is essential for microglial function, the cellular source of TGF-ß1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-ß1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-ß1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-ß1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-ß1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cognição
/
Microglia
/
Camundongos Knockout
/
Comunicação Autócrina
/
Fator de Crescimento Transformador beta1
/
Homeostase
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article