Heart and vascular responses across the lifespan in Ts65Dn mice, a model of Down syndrome

摘要 唐氏综合症（Ds）是智力残疾的最常见的染色体原因， 21号染色体基因的三倍。D患者表现出认知缺陷， 阿尔茨海默病（AD）的发展。Ds的良好表征的小鼠模型是Ts 65 Dn小鼠。 该模型在6个月龄时具有指示AD的神经解剖学变化， 6至11个月的赤字。除了认知异常，在Ds，共病包括 由自主神经系统介导的心血管改变。具体目标1 父母奖将比较WT和Ts 65 Dn小鼠的心血管概况和血管生理学， 3、6和12个月龄。自主神经张力将通过心率进行操作定义和测量 可变性该补充申请计划检查这些小鼠的行为测量。 在测试之前，将进行巴恩斯迷宫、新物体识别、旷场和高架十字迷宫。 每个年龄组的心血管实验。这些拟议的调查涉及NICHD主题 “唐氏综合症患者患阿尔茨海默病的风险显著增加” 在NOT-AG-20-3中列出。Ts 65 Dn在早期发育中有认知缺陷，然后采取一些措施， 例如空间学习和记忆，在随后的几个月里会恶化。这些恶化的行为指标是 被认为代表Ts 65 Dn中行为和外向AD或其他痴呆的表现。在 在这个补充中，我们计划将行为测试与心率变异性测量相关联。降低高 频率心率变异性指示较低的副交感神经张力。在一些人类研究中， 高频心率变异性（较低的副交感神经张力）对应于认知障碍。 我们之前已经发表，Ts 65 Dn也具有较低的高频心率变异性（较低的心率变异性）。 副交感神经张力）。由于行为变化表明AD存在于6- 在Ts 65 Dn中11个月，我们假设心率变异性变化将相关，甚至先于 行为该补充计划调查心率变异性是否可用作非侵入性 标志物来确定AD的前驱期。

ABSTRACT Down Syndrome (Ds) is the most common chromosomal cause of intellectual disability and results from triplication of chromosome 21 genes. Persons with Ds demonstrate cognitive deficits and early development of Alzheimer’s disease (AD). A well-characterized mouse model of Ds is the Ts65Dn mouse. This model has neuroanatomical changes indicative of AD by 6 months of age and worsening behavioral deficits between 6 and 11 months. In addition to cognitive abnormalities in Ds, co-morbidities include cardiovascular alterations that are mediated by the autonomic nervous system. Specific Aim 1 of the parent award will compare the cardiovascular profile and vascular physiology of WT and Ts65Dn mice at 3, 6 and 12 months of age. Autonomic tone will be operationally defined and measured by heart rate variability. This supplemental application plans to examine behavioral measures in these same mice. Barnes maze, novel object recognition, open field, and elevated plus maze will be performed prior to the cardiovascular experiments for each age group. These proposed investigations address the NICHD topic of interest “The significantly increased risk of Alzheimer’s disease in adults with Down syndrome” listed in NOT-AG-20-3. Ts65Dn has cognitive deficits in early development and then some measures, such as spatial learning and memory, worsen in later months. These worsening behavioral measures are considered to represent the presentation of behavior and outwards AD or other dementia in Ts65Dn. In this supplement, we plan to correlate behavioral tests with heart rate variability measures. Lower high frequency heart rate variability is indicative of lower parasympathetic tone. In some human studies, lower high frequency heart rate variability (lower parasympathetic tone) corresponds to cognitive impairment. We have previously published that Ts65Dn also has lower high frequency heart rate variability (lower parasympathetic tone) at 9 months of age. Since behavioral changes indicative of AD present between 6- 11 months in Ts65Dn, we hypothesize that heart rate variability changes will correlate, or even precede the behavior. This supplement plans to investigate if heart rate variability could be used as a non-invasive marker to determine the prodromal phase of AD.