Hunter Christopher L, Bimonte-Nelson Heather A, Nelson Mathew, Eckman Christopher B, Granholm Ann-Charlotte
Department of Physiology and Neuroscience and the Center on Aging, Medical University of South Carolina, 26 Bee Street, Charleston, SC 29425, USA.
Neurobiol Aging. 2004 Aug;25(7):873-84. doi: 10.1016/j.neurobiolaging.2003.10.010.
Individuals with Down's syndrome (DS) develop neuropathological features similar to Alzheimer's disease (AD) early in life, including dementia, accumulation of beta-amyloid, and irregular phosphorylation of tau proteins. Ts65Dn mice, an animal model of DS, provide a unique method to investigate the mechanisms related to AD-like symptoms in DS and possible therapeutic interventions. Ts65Dn mice undergo a decline in cholinergic phenotype and cognitive deterioration beginning at 6-8 months of age. In middle-aged female Ts65Dn mice, estrogen supplementation alleviated these cholinergic and cognitive impairments. The current study investigated AD-like markers and the effects of estrogen in male Ts65Dn mice. Estrogen treatment prior to behavioral testing did not improve cognitive deficits in 6-month-old male Ts65Dn mice, but decreased total and phosphorylated (pS199) tau in the entorhinal cortex compared to normosomic animals. Hippocampal beta-amyloid(1-42) levels were increased in Ts65Dn animals, regardless of estrogen treatment. These findings further support Ts65Dn mice as a model for specific AD-like symptoms, and demonstrate that estrogen treatment of this type does not improve the cognitive ability of male Ts65Dn mice.
唐氏综合征（DS）患者在生命早期就会出现与阿尔茨海默病（AD）相似的神经病理学特征，包括痴呆、β-淀粉样蛋白积累和tau蛋白的异常磷酸化。Ts65Dn小鼠是DS的动物模型，为研究DS中与AD样症状相关的机制以及可能的治疗干预提供了独特的方法。Ts65Dn小鼠在6至8个月大时开始出现胆碱能表型下降和认知能力恶化。在中年雌性Ts65Dn小鼠中，补充雌激素可缓解这些胆碱能和认知障碍。当前的研究调查了雄性Ts65Dn小鼠中的AD样标志物以及雌激素的作用。在行为测试前进行雌激素治疗并没有改善6个月大的雄性Ts65Dn小鼠的认知缺陷，但与正常染色体动物相比，降低了内嗅皮质中总tau和磷酸化（pS199）tau的水平。无论是否接受雌激素治疗，Ts65Dn动物海马中的β-淀粉样蛋白（1-42）水平均升高。这些发现进一步支持Ts65Dn小鼠作为特定AD样症状的模型，并表明这种类型的雌激素治疗并不能提高雄性Ts65Dn小鼠的认知能力。
