Estrogen Receptor β Protects Against ASD-like Behavior in Mice
Objectives: This study aims to determine whether estrogen receptor β signaling can protect against endoplasmic reticulum (ER) stress induced behavioral deficits in mice.
Methods: ER stress was induced by administering tunicamycin (1mg/kg I.P.) to mice. Protein levels were measured by western blot analysis whereas RT-PCR was used for gene expression analysis. Behavioral tests were performed including ultrasonic vocalization recordings, social interaction test, grooming test, marble bury test, forced swim test, tail suspension test, and open field test. The role of ERβ was examined by pharmacological as well as genetic manipulations in mice.
Results: We found that ER stress in mice reduces ERβ signaling in mouse frontal cortex. ER stress induced ASD-like behavior such as social deficits, depressive-like behavior, increases in obsessive behaviors, and communication deficits. Moreover, boosting ERβ signaling could reverse ER stress-induced deficits in ASD-like behavior in mice.
Conclusions: ERβ is a possible target for treatment of ASD and related neurodevelopmental disorders.