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

Ts65Dn 小鼠（唐氏综合症模型）整个生命周期中心脏和血管的反应

基本信息

批准号：
10404845
负责人：
Lara Roberts Deruisseau
金额：
$ 11.25万
依托单位：
SYRACUSE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2022-08-31
项目状态：
已结题

项目摘要

ABSTRACT Down Syndrome (Ds) is the most common chromosomal cause of intellectual disability and results from triplication of chromosome 21 genes. Individuals with Ds also have cardiovascular and autonomic challenges. We have published data showing lower blood pressure and heart rate in Ts65Dn, an accepted mouse model of Ds. Additionally, we also demonstrated altered autonomic function in Ts65Dn vs. WT. Therefore, Ts65Dn is an appropriate model to investigate cardiovascular and autonomic function in Ds. Finding ways to improve cardiovascular and autonomic function would influence the lives of individuals with Ds. Exercise is a feasible and accessible intervention that results in enhanced cardiac outcomes and autonomic function in other populations. Limited reports demonstrate exercise therapy also has positive autonomic results for individuals with Ds. Additional controlled, larger cohort studies investigating the influence of chronic exercise on blood pressure, heart rate and autonomic function are important for the Ds population. This supplement proposes to conduct the initial exercise studies using a mouse model, Ts65Dn. The parent award will determine mechanisms of cardiovascular and autonomic function in Ts65Dn. 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. This supplemental application plans to examine the role of wheel running exercise in WT and Ts65Dn on the cardiovascular and autonomic profile in these mice at 3 and 6 months of age. The supplemental exercised mouse groups will be compared to the parent award non-exercised groups (WT and Ts65Dn) from Aim 1. We hypothesize that exercise will improve autonomic function in both WT and Ts65Dn, but will likely have a stronger influence on Ts65Dn cardiovascular outcomes. These proposed investigations address the NICHD funding priority “studies of rodent models to understand cognition, behavior, and other aspects of the phenotype across different stages of development”. Overall, this supplement plans to investigate if lifelong exercise is a safe and effective intervention for cardiovascular and autonomic function in Ts65Dn, and by clinical correlate, Ds.

抽象的唐氏综合症 (Ds) 是导致智力障碍的最常见染色体原因，其结果是 21号染色体基因的三倍体。患有 D 的个体也有心血管和自主神经挑战。我们发表的数据显示 Ts65Dn 具有较低的血压和心率，Ts65Dn 是公认的 Ds.小鼠模型此外，我们还证明了 Ts65Dn 与 WT 相比自主功能的改变。因此，Ts65Dn 是研究 Ds 心血管和自主神经功能的合适模型。寻找改善心血管和自主神经功能的方法将影响个人的生活与 D。运动是一种可行且容易获得的干预措施，可以改善心脏结局，其他人群的自主功能。有限的报告表明运动疗法也有积极作用 Ds 患者的自主神经结果。其他对照、规模更大的队列研究调查了长期运动对血压、心率和自主神经功能的影响对于 Ds 人口。本补充建议使用小鼠模型进行初步运动研究， Ts65Dn。家长奖将确定心血管和自主神经功能的机制 Ts65Dn。家长奖的具体目标 1 将比较心血管状况和血管状况 3、6 和 12 个月龄 WT 和 Ts65Dn 小鼠的生理学。该补充申请计划检查 WT 和 Ts65Dn 中的轮跑运动对心血管和自主神经的作用这些小鼠在 3 个月和 6 个月大时的概况。补充运动小鼠组将是与目标 1 中的父母奖励非行使组（WT 和 Ts65Dn）相比。我们假设运动会改善 WT 和 Ts65Dn 的自主神经功能，但可能会产生更强的影响 Ts65Dn 心血管结局。这些拟议的调查涉及 NICHD 的资助优先事项 “研究啮齿动物模型以了解认知、行为和表型的其他方面不同的发展阶段”。总体而言，本补充计划调查终身锻炼是否安全以及对 Ts65Dn 心血管和自主神经功能的有效干预，并通过临床关联， Ds。