脑脊髓液驱动的表皮运动乳头缺陷与多发性硬化症有关
Maxime Bigotte1, Adam M R Groh1, Elia Afanasiev1
1Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, H3A 2B4, Canada.
Brain : a journal of neurology
|November 24, 2025
概括
在多发性硬化症 (MS) 中,垂体细胞纤维被破坏,影响脑脊液 (CSF) 流动,并导致大脑病理. 这项研究揭示了MS中的毛功能障碍及其在疾病进展和行为症状中的潜在作用.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 多发性硬化症 (MS) 涉及中枢神经系统 (CNS) 的自身免疫性攻击,导致脱髓化和焦点病变.
- 扩散的表面入病理梯度表明脑脊液 (CSF) 因素有助于MS进展,特别是在CSF接触区域.
- 垂体细胞,内膜心室,具有对CSF恒温至关重要的运动性纤维,但它们在MS中的作用仍然未被探索.
研究的目的:
- 在多发性硬化症 (MS) 的背景下研究表皮细胞的作用和影响.
- 确定在多发性硬化症患者和动物模型中是否存在表皮毛的失调.
- 评估多发性硬化症上垂体纤维干扰的细胞和行为后果.
主要方法:
- 从多发性硬化症患者和对照人群中获得的人类末端细胞的单细胞RNA测序.
- 培养的动物上部细胞暴露于MS患者的CSF.
- 在实验性自身免疫性脑膜炎 (EAE) 鼠标模型中对表皮毛的分析.
- 一个转基因小鼠模型的生成,具有有条件的表肠状干扰.
主要成果:
- 单细胞RNA测序揭示了MS患者人类内皮细胞中纤毛基因的显著失调.
- 多发性硬化症患者的CSF暴露改变了表皮细胞的状基因/蛋白质表达,并减少了殴打频率.
- 在EAE模型中的垂体细胞表现出膜基因和蛋白质表达的改变;在MSCSF中的IFNγ影响了膜运动.
- 在小鼠表皮细胞中Ccdc39的条件淘汰导致心室扩大,微质密度增加和行为变化.
结论:
- 在中枢神经系统自身免疫性中,表皮细胞的移动性毛是失调的,特别是在多发性硬化症中.
- 垂体乳毛的破坏可能会导致MS中的周周结膜病理.
- 干扰的表皮毛可能是MS的行为缺陷和非运动症状的基础.
更多相关视频
09:01Flow Cytometric Analysis of Lymphocyte Infiltration in Central Nervous System during Experimental Autoimmune Encephalomyelitis
Published on: November 17, 2020
7.7K
10:50Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
8.2K
相关概念视频
01:05Mechanism of Ciliary Motion
4.8K
The ciliary structures were first seen in 1647 by Antonie Leeuwenhoek while observing the protozoans. In lower organisms, these appendages are responsible for cell movement, while in higher organisms, these appendages help in the movement of the extracellular fluids within the body cavities.
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
The cilia are made up of microtubules in a 9+2 arrangement, with nine microtubule doublet ring bundles, surrounding a pair of central singlet microtubule bundles. The doublet microtubule bundles are...
4.8K
01:21Cerebrospinal Fluid
5.1K
Cerebrospinal fluid (CSF) is a colorless liquid that flows around the brain and the spinal cord, playing a vital role in the protection, support, and overall function of the central nervous system (CNS). CSF production, circulation, and absorption are tightly regulated processes essential for the brain and spinal cord to function properly.
CSF Production
CSF is produced mainly in the choroid plexus, a network of capillaries and ependymal cells located within the ventricular system of the brain....
CSF Production
CSF is produced mainly in the choroid plexus, a network of capillaries and ependymal cells located within the ventricular system of the brain....
5.1K
01:23Transcellular Transport of Solutes
4.6K
Transcellular transport of solutes is the movement of substances like monosaccharides and amino acids through polarized cells. This transport mechanism is primarily seen in epithelial and endothelial cells aided by membrane transport proteins such as channels and transporters. The tight junctions between these cells confine the membrane proteins to the two sides of the cell. The epithelial cells have distinct apical and basolateral domains. In contrast, the endothelial cells show the luminal...
4.6K
01:22Microtubules in Signaling
2.1K
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
2.1K