Farr Susan A, Banks William A, Uezu Kayoko, Gaskin F Spencer, Morley John E
Geriatric Research Education and Clinical Center (GRECC), VA Medical Center, St. Louis, MO, USA.
Life Sci. 2004 Oct 22;75(23):2775-85. doi: 10.1016/j.lfs.2004.05.026.
Dehydroepiandrosterone sulfate (DHEAS) has been reported to improve memory in aged animals and suggested as a treatment for age-related dementias. The SAMP8 mouse, a model of Alzheimer's disease, has an age-related impairment in learning and memory and an increase in brain levels of amyloid precursor protein (APP) and amyloid beta protein (Abeta). Male SAMP8 mice also have a decrease in testosterone, to which DHEA is a precursor. Diabetes has been suggested as a model of aging and to be linked to Alzheimer's disease. Diabetics can have memory deficits and lower DHEAS levels. Here, we examined the effects of chronic oral DHEAS on acquisition and retention for T-maze footshock avoidance in 12 mo male SAMP8 mice and in CD-1 mice with streptozocin-induced diabetes. Learning and memory were improved in aged SAMP8 mice, but not in CD-1 mice with streptozocin-induced diabetes. These findings suggest that DHEAS is more effective in reversing the cognitive impairments associated with overexpression of Abeta than with diabetes.
硫酸脱氢表雄酮（DHEAS）已被报道可改善老年动物的记忆力，并被建议作为治疗与年龄相关痴呆症的药物。SAMP8小鼠是阿尔茨海默病模型，存在与年龄相关的学习和记忆障碍，且脑内淀粉样前体蛋白（APP）和淀粉样β蛋白（Aβ）水平升高。雄性SAMP8小鼠的睾酮水平也降低，而DHEA是睾酮的前体。糖尿病被认为是衰老的一种模型，且与阿尔茨海默病有关。糖尿病患者可出现记忆缺陷和较低的DHEAS水平。在此，我们研究了慢性口服DHEAS对12月龄雄性SAMP8小鼠以及链脲佐菌素诱导糖尿病的CD-1小鼠在T迷宫足部电击回避实验中的获得和保持的影响。老年SAMP8小鼠的学习和记忆能力得到改善，但链脲佐菌素诱导糖尿病的CD-1小鼠则没有。这些发现表明，DHEAS在逆转与Aβ过表达相关的认知障碍方面比在糖尿病方面更有效。
