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

Ruiyu ZHANG; Tianyao LIU; Rui XIAO; Xiaotang FAN

doi:10.16016/j.1000-5404.201811078

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

Basic Medicine | 更新时间：2026-01-09

- Estrogen receptor β agonist ameliorates social deficits in a mouse model of autism
- Journal of Third Military Medical University Vol. 41, Issue 6, Pages: 507-513(2019)
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)医学心理系军事认知心理学教研室
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(31871043)
- DOI：10.16016/j.1000-5404.201811078
  CLC： R-332; R749.91; R977.12
- Received：12 November 2018，
  
  Revised：2018-12-24，
  
  Published：30 March 2019
- 稿件说明：
移动端阅览
Ruiyu ZHANG, Tianyao LIU, Rui XIAO, et al. Estrogen receptor β agonist ameliorates social deficits in a mouse model of autism[J]. Journal of Third Military Medical University, 2019, 41(6): 507-513.
DOI：

Ruiyu ZHANG, Tianyao LIU, Rui XIAO, et al. Estrogen receptor β agonist ameliorates social deficits in a mouse model of autism[J]. Journal of Third Military Medical University, 2019, 41(6): 507-513. DOI： 10.16016/j.1000-5404.201811078.

摘要

目的

探讨雌激素β受体特异性激动剂ly3201对自闭症模型BTBR小鼠的行为改善作用。

方法

将健康同窝C57BL/6J(C57)、BTBR小鼠分为4组：C57生理盐水组、C57药物处理组、BTBR生理盐水组、BTBR药物处理组；小鼠生后2 d，药物处理组腹腔注射雌激素β受体激动剂ly3201(1.6 mg/kg)，生理盐水组腹腔注射等量生理盐水；于生后14 d采用荧光定量PCR和免疫组化检测各组小鼠皮层与海马内雌激素β受体的表达；于小鼠2月龄进行自闭症相关行为学检测。

结果

生后14 d，BTBR生理盐水组皮层与海马内雌激素β受体的表达显著低于C57生理盐水组(

0.05)，而ly3201处理则上调了C57与BTBR小鼠皮层及海马内雌激素β受体的表达(

0.01)。在三箱社交实验中，BTBR药物处理组小鼠在小鼠箱体停留时间大于在物体箱体中停留时间(

0.05)，对小鼠的嗅探时间大于对物体的嗅探时间(

0.05)；并且统计箱体时间(

0.01)和嗅探时间(

0.01)偏好系数也显示BTBR药物处理组表现出对小鼠的明显偏好；在交互实验中，BTBR药物处理组鼻对鼻嗅探时间(

0.05)、鼻对会阴嗅探时间(

0.05)明显多于BTBR生理盐水组，而其对箱体探索时间明显少于BTBR生理盐水组(

0.05)。

结论

雌激素β受体激动剂ly3201激活海马与皮层内源性雌激素β受体的表达，显著改善BTBR自闭症模型小鼠的社交缺陷。

Abstract

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 (

0.05)

and treatment with ly3201 obviously enhanced estrogen receptor β expression in both BTBR and C57 mice (

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 (

0.05); they also spent significantly longer time for exploratory sniffing of other mice than of the new object (

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 (

0.05) and anogenital sniffing (

0.05) with a significantly reduced time for cage exploration (

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.

关键词

Keywords

references

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