Chemogenetic manipulation of CX3CR1 + cells transiently induces hypolocomotion independent of microglia.
Shunyi ZhaoJiaying ZhengLingxiao WangAnthony D UmpierreSebastian ParuselManling XieAastha DheerKatayoun AyasoufiAaron J JohnsonJason R RichardsonLong Jun WuPublished in: Molecular psychiatry (2023)
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.
Keyphrases
- induced apoptosis
- inflammatory response
- neuropathic pain
- cell cycle arrest
- biofilm formation
- data analysis
- high glucose
- diabetic rats
- drug induced
- poor prognosis
- endoplasmic reticulum stress
- signaling pathway
- oxidative stress
- staphylococcus aureus
- type diabetes
- adipose tissue
- high fat diet induced
- escherichia coli
- spinal cord
- skeletal muscle