雌激素对app/ps1双转基因阿尔茨海默病模型小鼠海马老年斑形成的抑制作用

Estrogen inhibiting neuritic plaque formation in hippocampus of app/ps1 double transgenic mice of Alzheimer’s disease

目的 :用无偏性体视学定量研究雌激素对app/ ps1双转基因 (app/ ps1dtg)AD模型小鼠海马β 淀粉样蛋白 (Aβ)沉积及老年斑形成的抑制作用。方法 :雌性app/ ps1dtg小鼠行双侧卵巢切除 ,于颈部皮下植入可持续释放 6 0d的 17β 雌二醇片剂 (17 βestradiol,E2 ) ;6 0d后取脑行冰冻切片 ,6E10免疫组化染色显示沉积于海马的Aβ ,刚果红组织学染色显示老年斑 ,无偏性体视学测量海马内Aβ斑及老年斑的总体积。结果 :E2抑制Aβ在海马内沉积 ,降低海马内Aβ斑的总体积 ,并抑制老年斑的形成。 结论 :E2防治阿尔茨海默病可能与E2抑制Aβ在脑内沉积并聚集形成老年斑有关。

Objective: To examine the inhibition e ffects of estrogen (E2) on Aβ deposition and neuritic plaque formation in hippocampus of the app/ps1 double transgenic (app/ps1 dtg) mice model for Alzheimer’s disease. Methods: Female app/ps1 dtg mice aged 15-17 months received bilateral ovariectomy followed by s.c. placement of 60-day release pellet containing 17-β estradiol (1.7 mg) or placebo (cholesterol). After 60 days treatment, the total volume of Aβ plaques and neuritic plaques were quantified by unbiased stereology in hippocampus using 6E10 immunohistochemistry and Congo red staining. Results: Long-term E2 treatment in app/ps1 dtg mice aged 15-17 months significantly inhibited Aβ deposition,lowered the total volume of Aβ positive plaques and compacted neuritic plaques in hippocampus. Conclusion: E2 treatment and prevention for Alzheimer’s disease may be due to its inhibition effect on Aβ deposition and compact neuritic plaques formation.