Estrogen receptor β agonist ameliorates social deficits in a mouse model of autism

Objective To explore the therapeutic effect of estrogen receptor β agonist ly3201 on autism-like behaviors in BTBR mice. Methods Healthy neonatal (2 days old) C57BL/6J(C57) and BTBR littermate mice were both divided into 2 groups and subjected to intraperitoneal injections of estrogen receptor β agonist ly3201 at the dose of 1.6 mg/kg or normal saline of an equivalent volume. We measured the expression levels of estrogen receptor β in the cerebral cortex and hippocampus of the mice on day 14 after birth with immunohistochemistry and real-time PCR, and tested the mice for autism-like behaviors at 2 months of age. Results At 14 d after birth, the expression levels of estrogen receptor β in the cerebral cortex and hippocampus were significantly lower in BTBR mice than in C57 mice (P < 0.05), and treatment with ly3201 obviously enhanced estrogen receptor β expression in both BTBR and C57 mice (P < 0.01). In the three-chambered social test, BTBR mice with ly3201 treatment spent significantly longer time in the chamber with other mice than in the chamber with a new object (P < 0.05); they also spent significantly longer time for exploratory sniffing of other mice than of the new object (P < 0.05). In the male-female reciprocal social interaction test, compared with the saline-treated mice, BTBR mice with ly3201 treatment exhibited longer time of nose-to-nose sniffing (P < 0.05) and anogenital sniffing (P < 0.05) with a significantly reduced time for cage exploration (P < 0.05). Conclusion Estrogen receptor β agonist ly3201 activates the expression of endogenous estrogen receptor in the hippocampus and cortex to alleviate social deficits in BTBR mice.