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）是智力障碍的最常见染色体原因，来自染色体21个基因的三分一式化。 DS患者也有心血管和自主教挑战。我们发布了显示较低的血压和心率的数据， DS的鼠标模型。此外，我们还证明了TS65DN与WT中的自主功能改变了。因此，TS65DN是研究DS中心血管和自主功能的合适模型。寻找改善心血管和自主功能的方法将影响个人的生活与DS。运动是可行且易于获得的干预措施，可增强心脏结果和其他人群中的自主功能。有限的报告表明运动疗法也有积极 DS患者的自主结果。其他受控的大型队列研究研究了慢性运动对血压，心率和自主功能的影响对于 DS人口。这项补充建议使用小鼠模型进行初步运动研究， TS65DN。父母奖将确定心血管和自主功能的机制 TS65DN。父母奖的特定目的1将比较心血管轮廓和血管 WT和TS65DN小鼠的生理学在3、6和12个月大。此补充申请计划检查在WT和TS65DN在心血管和自主教中的锻炼的作用这些小鼠在3和6个月大的小鼠中的剖面。补充运动的鼠标组将是与AIM 1的父母奖相比，非行使的群体（WT和TS65DN）。我们假设这是锻炼将改善WT和TS65DN的自主功能，但可能会有更强的影响在TS65DN心血管结局上。这些拟议的调查涉及NICHD资金优先 “啮齿动物模型的研究，以了解跨表型的认知，行为和其他方面总的来说，这种补充计划调查终身运动是否安全并有效干预TS65DN的心血管和自主功能，并通过临床相关性， DS。