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在老年雄性和雌性小鼠中,脑内出血后大脑蛋白质组发生变化

Sivaraman Kuppuswamy¹, Noah J Watson¹, William Luke Ledford¹

¹Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, 1120, 15th Street, CB3515, Augusta, GA 30912, United States of America.

Neurobiology of disease

|May 4, 2025

概括

衰老显著改变了脑内脑出血 (ICH) 后的大脑蛋白质变化. 这项研究确定了老年小鼠ICH病理中的关键蛋白质和途径,突出了线粒体功能障碍和性别特异性差异.

科学领域:

神经科学是一个神经科学.
蛋白质组学是指蛋白质组学.
老年学是一门学科.

背景情况:

衰老是脑内出血 (ICH) 后不良结果的主要危险因素.
对老年患者和ICH病理生理学的临床前研究是有限的.
了解老龄化人口中的ICH是非常重要的,因为发生率越来越高.

研究的目的:

在ICH之后,在老年小鼠中表征大脑蛋白质基因变化.
为了研究蛋白质组对ICH反应的性别特异性差异.
确定潜在的治疗点,并了解老化中的ICH病理生物学.

主要方法:

在老年雄性和雌性小鼠 (18-24个月) 上使用无标签的定量蛋白质组 (LC-MS/MS),接受假/ICH.
在手术后3天分析了双侧脑组织,将性别视为生物变量.
通过免疫组织化学和西斑验证的质谱数据,随后进行生物信息学分析.

主要成果:

在老年雄性小鼠中鉴定出133种差异表达蛋白 (DEP) (98种下调,35种上调).
在老年雌性小鼠中确定了315个DEP (221个下调,94个上调).
突出显示14-3-3蛋白和S100-A9作为ICH病理中的潜在关键DEP;在ICH诱导的大脑损伤中表明线粒体功能障碍.

结论:

老龄化对ICH后的蛋白质组景观产生了深远的影响,性别差异很大.
线粒体功能障碍成为老年人ICH后急性脑损伤的关键因素.
蛋白质组数据为未来的功能研究和老龄化人口中ICH的治疗开发提供了基础.

关键词:

衰老的衰老衰老的衰老生物信息学是一种生物信息学.血液瘤是一种血液瘤.脑内出血脑内出血质谱测量质量谱测量

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