Journal Article

Chemogenetic manipulation of CX3CR1+ cells transiently induces hypolocomotion independent of microglia

Wu, Long-Jun, Johnson, Aaron J., Zhao, Shunyi, Dheer, Aastha, Parusel, Sebastian, Ayasoufi, Katayoun, Richardson, Jason R., Wang, Lingxiao, Zheng, Jiaying, Umpierre, Anthony D., Xie, Manling

2023

Overview

Chemogenetic approaches using Designer Receptors Exclusively Activated by Designer Drugs (DREADD, a family of engineered GPCRs) were recently employed in microglia. Here, we used Cx3cr1 CreER/+ :R26 hM4Di/+ 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 Tmem119 CreER/+ :R26 hM4Di/+ 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 Cx3cr1 CreER/+ mouse line to manipulate microglia.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 14 / 14/35 / 42 / 42/35 / 631/378 / 631/80 / 64 / 64/60 / 96 / 96/31 / Animals / Anxiety / Behavior / Behavioral Sciences / Biological Psychology / CD4 antigen / Cell activation / CX3CR1 protein / Flow cytometry / Gender differences / Immediate Communication / Immunosuppressive agents / Lymphocytes T / Macrophages / Medicine / Medicine & Public Health / Mice / Microglia / Motor ability / Neurons - metabolism / Neurosciences / Pharmacotherapy / Proteins / Psychiatry