Chemogenetic manipulation of CX3CR1+ cells transiently induces hypolocomotion independent of microglia.
Mol Psychiatry
; 28(7): 2857-2871, 2023 Jul.
Article
em En
| MEDLINE
| ID: mdl-37365239
ABSTRACT
Chemogenetic approaches using Designer Receptors Exclusively Activated by Designer Drugs (DREADD, a family of engineered GPCRs) were recently employed in microglia. Here, we used Cx3cr1CreER/+R26hM4Di/+ mice to express Gi-DREADD (hM4Di) on CX3CR1+ cells, comprising microglia and some peripheral immune cells, and found that activation of hM4Di on long-lived CX3CR1+ cells induced hypolocomotion. Unexpectedly, Gi-DREADD-induced hypolocomotion was preserved when microglia were depleted. Consistently, specific activation of microglial hM4Di cannot induce hypolocomotion in Tmem119CreER/+R26hM4Di/+ mice. Flow cytometric and histological analysis showed hM4Di expression in peripheral immune cells, which may be responsible for the hypolocomotion. Nevertheless, depletion of splenic macrophages, hepatic macrophages, or CD4+ T cells did not affect Gi-DREADD-induced hypolocomotion. Our study demonstrates that rigorous data analysis and interpretation are needed when using Cx3cr1CreER/+ mouse line to manipulate microglia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Microglia
/
Neurônios
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos