Berry Anne, Tomidokoro Yasushi, Ghiso Jorge, Thornton Jan
Neuroscience Department, Oberlin College, 119 Woodland Street, Oberlin, OH 44074, USA.
Horm Behav. 2008 Jun;54(1):143-52. doi: 10.1016/j.yhbeh.2008.02.006. Epub 2008 Mar 10.
Numerous studies have suggested that estradiol (E) improves spatial memory as female rats with E perform better than those without E. However there is an inverse relationship between E and luteinizing hormone (LH) levels and LH could play a role. We examined whether treatment with the LH homologue human chorionic gonadotropin (hCG), would impair spatial memory of adult E-treated female rats. In the object location memory task, ovariectomized (ovxed) rats treated with E and either a single high dose (400 IU/kg) or a lower repeated dose of hCG (75 IU/kg hourly for 8 h) showed spatial memory disruption compared to ovxed rats treated with estradiol alone. Impairment was attributed to memory disruption as performance improved with shortened delay between task exposure and testing. Tests on another spatial memory task, the Barnes maze, confirmed that hCG (400 IU/kg) can impair memory: although E+veh treated animals made significantly fewer hole errors across time, E+hCG-treated did not. In humans, high LH levels have been correlated with Alzheimer's disease (AD). Because brain amyloid-beta (Abeta) species have been implicated as a toxic factor thought to cause memory loss in AD, we analyzed whether hCG-treated animals had increased Abeta levels. Levels of Abeta from whole brains or hippocampi were assessed by Western blot. hCG treatment to E-implanted females significantly increased soluble Abeta40 and Abeta42 levels. These results indicate that high levels of LH/hCG can impair spatial memory, and an increase in brain Abeta species may account for the memory impairment in hCG-treated rats.
大量研究表明,雌二醇(E)可改善空间记忆,因为接受E治疗的雌性大鼠比未接受E治疗的大鼠表现更好。然而,E与促黄体生成素(LH)水平之间存在负相关关系,LH可能起作用。我们研究了用LH同源物人绒毛膜促性腺激素(hCG)治疗是否会损害成年E治疗雌性大鼠的空间记忆。在物体位置记忆任务中,与仅接受雌二醇治疗的去卵巢(ovxed)大鼠相比,接受E和单次高剂量(400 IU/kg)或较低重复剂量hCG(每小时75 IU/kg,共8小时)治疗的去卵巢大鼠表现出空间记忆障碍。这种损害归因于记忆破坏,因为随着任务暴露和测试之间延迟时间的缩短,表现有所改善。在另一项空间记忆任务——巴恩斯迷宫测试中,证实hCG(400 IU/kg)会损害记忆:尽管接受E+载体治疗的动物随着时间推移犯的洞错误明显减少,但接受E+hCG治疗的动物却没有。在人类中,高LH水平与阿尔茨海默病(AD)相关。由于脑淀粉样β蛋白(Aβ)被认为是导致AD记忆丧失的毒性因素,我们分析了接受hCG治疗的动物Aβ水平是否升高。通过蛋白质免疫印迹法评估全脑或海马体中的Aβ水平。对植入E的雌性动物进行hCG治疗显著提高了可溶性Aβ40和Aβ