Baboon model of chemotherapy-related cognitive impairment and accelerated aging

化疗相关认知障碍和加速衰老的狒狒模型

基本信息

项目摘要

Project Summary Chemotherapy is an extremely effective treatment for cancer; however, along with chemotherapy’s benefits there are many undesirable consequences including chemotherapy-related cognitive impairments (CRCI) and accelerated aging. Despite impacts on quality of life, these areas are relatively understudied and there are currently no FDA approved treatments available. A sophisticated animal model to address this problem will be extremely valuable, both to our understanding of the long-term consequences and to the development of potential treatments. Currently, CRCI and chemotherapy-related accelerated aging is studied in rodents, but a nonhuman primate model will significantly enhance the validity of studies addressing this still under-researched phenomenon. In this proposed study, we aim to establish a baboon model of CRCI and accelerated aging. We will further define healthy aging in a baboon sample, then investigate whether chemotherapy induces cognitive decline and accelerates brain aging in baboons as it does in humans and test an intervention which has been effective in mice. We will collect brain imaging, cognitive, and aging molecular biomarker data from baboons prior to treatment with cisplatin only or cisplatin followed by an HDAC6 inhibitor. We will then collect further brain, cognitive, and aging data post-treatment to examine changes related to the chemotherapy regimen and whether the HDAC6 inhibitor reverses cognitive declines and neurodegeneration. These data will be used to propose further studies as well as techniques to potentially mitigate these consequences of chemotherapy in humans.
项目概要 化疗是一种极其有效的癌症治疗方法。然而,除了化疗的好处 有许多不良后果,包括化疗相关的认知障碍(CRCI)和 加速老化。尽管对生活质量有影响,但这些领域的研究相对不足,并且存在 目前尚无 FDA 批准的治疗方法。解决这个问题的复杂动物模型将是 对于我们了解长期后果和发展 潜在的治疗方法。目前,CRCI 和化疗相关的加速衰老正在啮齿类动物中进行研究,但 非人类灵长类动物模型将显着提高解决这一仍待研究的问题的研究的有效性 现象。在这项拟议的研究中,我们的目标是建立 CRCI 和加速衰老的狒狒模型。我们 将进一步定义狒狒样本中的健康衰老,然后研究化疗是否会诱导认知能力 与人类一样,狒狒的大脑老化程度下降并加速,并测试了一种干预措施 对小鼠有效。我们将从狒狒身上收集大脑成像、认知和衰老分子生物标志物数据 在仅使用顺铂治疗之前或在顺铂随后使用 HDAC6 抑制剂治疗之前。之后我们会进一步收集 治疗后的大脑、认知和衰老数据,以检查与化疗方案相关的变化 HDAC6 抑制剂是否可以逆转认知能力下降和神经退行性变。这些数据将用于 提出进一步的研究以及技术来潜在地减轻化疗的这些后果 人类。

项目成果

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Michele M Mulholland其他文献

Gray matter volume and asymmetry in Broca's and Wernicke's area homologs in chimpanzees (emPan troglodytes/em) using a probabilistic region of interest approach
使用感兴趣区域概率法研究黑猩猩(倭黑猩猩)布罗卡区和韦尼克区同源区域的灰质体积和不对称性
  • DOI:
    10.1016/j.neuroimage.2025.121038
  • 发表时间:
    2025-02-15
  • 期刊:
  • 影响因子:
    4.500
  • 作者:
    William D Hopkins;Muhammad A Spocter;Michele M Mulholland;Chet C Sherwood
  • 通讯作者:
    Chet C Sherwood

Michele M Mulholland的其他文献

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{{ truncateString('Michele M Mulholland', 18)}}的其他基金

Baboon model of chemotherapy-related cognitive impairment and accelerated aging
化疗相关认知障碍和加速衰老的狒狒模型
  • 批准号:
    10505742
  • 财政年份:
    2022
  • 资助金额:
    $ 18.98万
  • 项目类别:

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