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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease
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CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease

机译：CBP基因转移增加了BDNF的水平并改善了阿尔茨海默氏病小鼠模型的学习和记忆缺陷

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摘要

Cognitive dysfunction and memory loss are common features of Alzheimer's disease (AD). Abnormalities in the expression profile of immediate early genes that play a critical role in memory formation, such as the cAMP-response element binding protein (CREB), have been reported in the brains of AD patients. Here we show that amyloid-p (Aβ) accumulation, which plays a primary role in the cognitive deficits of AD, interferes with CREB activity. We further show that restoring CREB function via brain viral delivery of the CREB-binding protein (CBP) improves learning and memory deficits in an animal model of AD. Notably, such improvements occur without changes in Aβ and tau pathology, and instead are linked to an increased level of brain-derived neurotrophic factor. The resulting data suggest that A|i-induced learning and memory deficits are mediated by alterations in CREB function, based on the finding that restoring CREB activity by directly modulating CBP levels in the brains of adult mice is sufficient to ameliorate learning and memory. Therefore, increasing CBP expression in adult brains may be a valid therapeutic approach not only for AD, but also for various brain disorders characterized by alterations in immediate early genes, further supporting the concept that viral vector delivery may be a viable therapeutic approach in neurode-generative diseases.
机译：认知功能障碍和记忆力减退是阿尔茨海默氏病（AD）的常见特征。在AD患者的大脑中，已经报道了在记忆形成中起关键作用的立即早期基因的表达谱异常，例如cAMP反应元件结合蛋白（CREB）。在这里，我们显示淀粉样蛋白p（Aβ）积累，在AD认知缺陷中起主要作用，干扰CREB活性。我们进一步表明，通过CREB结合蛋白（CBP）的脑病毒传递恢复CREB功能可改善AD动物模型的学习和记忆缺陷。值得注意的是，这种改善发生在Aβ和tau病理没有改变的情况下，而是与脑源性神经营养因子水平的提高有关。结果发现，通过直接调节成年小鼠大脑中的CBP水平来恢复CREB活性足以改善学习和记忆能力，这一发现表明，A | i诱导的学习和记忆功能障碍是由CREB功能的改变引起的。因此，增加成年大脑中CBP的表达不仅可能是AD的有效治疗方法，而且对于以早期早期基因改变为特征的各种脑部疾病也可能是一种有效的治疗方法，进一步支持病毒载体递送可能是神经元疾病中可行的治疗方法的概念。生殖疾病。

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  • 作者

    Antonella Caccamo; Monica A. Maldonado; Alex F. Bokov; Smita Majumder; Salvatore Oddo;

  • 作者单位

    Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229,Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229;

    Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229,Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229;

    Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229,Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, TX 78229;

    Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229,Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229;

    Department of Physiology, University of Texas Health Science Center, San Antonio, TX 78229,Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX 78229;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    tangles; presenilin;

    机译：缠结;早老素;

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