More than microglial depletion: PLX5622 activates the hepatic constitutive androstane receptor to alter anesthesia and addiction - PubMed
5 hours ago
- #PLX5622
- #constitutive androstane receptor
- #microglial depletion
- PLX5622, a CSF1R inhibitor, is known for microglial depletion but has broader effects.
- PLX5622 activates the hepatic constitutive androstane receptor (CAR) in mice, inducing hepatic enzymes.
- This activation enhances metabolism and clearance of anesthetics and nicotine, affecting anesthesia sensitivity and addiction withdrawal.
- Transgenic microglial depletion did not replicate PLX5622's effects on anesthesia and addiction, indicating CAR's role.
- CAR inactivation nullified PLX5622's effects, showing its impact isn't solely due to microglial depletion.
- Findings caution the interpretation of PLX5622 treatment outcomes and guide future CSF1R inhibitor design.