肺高血压促进神经炎症和神经退行
Priscilla M De La Cruz1,2, Angelia Lockett1, Marta T Gomes1
1Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indiana University, Indianapolis.
bioRxiv : the preprint server for biology
|September 15, 2025
概括
肺动脉高血压 (PAH) 导致大脑变化,包括质细胞增加和神经元减少. 这项研究揭示了TDP-43蛋白在大脑中的错位,这是PAH的一个新发现.
科学领域:
- 神经科学是一个神经科学.
- 心血管科学 心血管科学
- 病理学 病理学 病理学
背景情况:
- 肺动脉高血压 (PAH) 与神经认知缺陷和大脑异常有关.
- 连接PAH与大脑病理的潜在机制尚不清楚.
- TDP-43蛋白病变与诸如FTLD和ALS等神经退行性疾病有关.
研究的目的:
- 研究与PAH相关的大脑神经病理变化的研究.
- 为了确定PAH是否会导致化,神经元密度降低和TDP-43错位.
- 为了检查TDP-43蛋白在人类PAH脑组织中的定位.
主要方法:
- 已建立的PAH老鼠模型使用单克罗他林或苏根/缺氧.
- 通过右心导管检查确认了PAH.
- 分析了微质 (Iba1),星球细胞 (GFAP),神经元 (NeuN) 和TDP-43.3的脑组织.
主要成果:
- 在PAH模型中,额叶皮层的微质和星细胞密度增加.
- 在PAH大鼠大脑中观察到神经元密度降低和神经元TDP-43错位.
- 人类PAH大脑样本也显示了神经元TDP-43错位.
结论:
- PAH会诱导神经病理变化,包括化和神经元损失.
- 这项研究提供了TDP-43蛋白质病变在肺动脉高血压中的第一个证据.
- 这些发现表明PAH和涉及TDP-43.3的神经退行过程之间的潜在联系.
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