老化治疗减轻了多克索鲁比诱导的化学大脑
Vivekananda Budamagunta1,2,3, Ashok Kumar1, Asha Rani1
1Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
Aging cell
|January 16, 2024
概括
化疗药物Doxorubicin (Dox) 通过释放进入大脑的外周衰老相关分泌表型 (SASP) 因素引起认知衰退. 一种老化药物ABT-263减轻了这些影响,这表明SASP因子和化学大脑之间存在联系.
科学领域:
- 神经科学是一个神经科学.
- 老年学是一门学科.
- 药理学 药理学是指药理学的学科.
背景情况:
- 化疗诱导的认知障碍,或化脑,与衰老有相似之处,包括炎症和氧化应激.
- 多克索鲁比 (Dox) 是一种常见的癌症药物,可以引起脑化学反应,但其直接进入大脑是有限的.
- 化学大脑的机制可能涉及外围细胞衰老和衰老相关分泌表型 (SASP) 因素的释放.
研究的目的:
- 调查多克索鲁比 (Dox) 如何影响老化和认知的外周和大脑标记物.
- 确定外围SASP因子是否可以进入大脑并诱导认知变化.
- 评估老化药物ABT-263在缓解Dox诱导的认知障碍方面的疗效.
主要方法:
- 给予多克索鲁比 (Dox) 来模拟化学大脑和衰老.
- 使用老化药物ABT-263进行治疗,该药物对大脑的透能力有限.
- 对外周等离子体和脑组织进行衰老标记,炎症,氧化应激和基因转录的分析.
- 评估突触功能和认知表现.
主要成果:
- 多克索鲁比治疗导致SASP因子释放到血中,随后进入大脑.
- 大脑暴露于SASP因子导致微质激活,氧化应激增加和基因转录改变.
- 对于记忆至关重要的突触功能由于改变的氧化还原信号受损.
- ABT-263治疗有效地预防或减少了多克斯诱导的大部分有害影响.
结论:
- 外围SASP因素在多克索鲁比诱导的认知衰退中发挥着重要作用.
- 这项研究强调了外围细胞衰老和化学大脑之间的机械联系.
- 这些发现表明Dox诱导的衰老和自然衰老过程之间存在相似之处和差异.
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