Department of Neurosciences Rita Levi Montalcini, University of Turin, 10126, Turin, Italy.
Schaller Research Group, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
Fluids Barriers CNS. 2023 Mar 14;20(1):19. doi: 10.1186/s12987-023-00420-9.
Choroid plexuses (ChPs) are intraventricular structures mainly composed by specialized epithelial cells interconnected by tight junctions that establish the blood-cerebrospinal fluid (CSF) barrier. ChPs are essential to produce CSF and transport solutes from and into the brain. Deterioration of ChP function and morphology has been correlated to worsening of neurodegenerative disorders. We here map morpho-functional changes in the ChP epithelial cells during healthy aging, starting from young adult to 2-years old mice.
We used a multi-tiered approach, including transmission electron microscopy (TEM), immunohistochemistry, RT-qPCR, Western Blot and 2-photon microscopy (2-PM) at multiple timepoints ranging from young adult to 2-years old mice.
We identified distinct morpho-functional modifications in epithelial cells of ChP starting from 8 to 12 months of age, which mostly remained stable up to 2 years. These changes include flattening of the epithelium, reduction of microvilli length and an augmentation of interrupted tight junctions. We also found a decrease in mitochondria density together with elongation of mitochondria in older mice. Morphological mitochondrial rearrangements were accompanied by increased superoxide levels, decreased membrane potential and decreased mitochondrial motility in aged mice. Interestingly, most of the age-related changes were not accompanied by modification of protein and/or gene expression levels and aged mitochondria effectively responded to acute pharmacological stressful stimuli.
Our study suggests a long-term progression of multiple morpho-functional features of the mouse choroid plexus epithelium during adulthood followed by structural remodeling during the aging process. These findings can lead to a better understanding on how functional and morphological rearrangements of ChP are correlated during aging.
脉络丛（ChP）是主要由通过紧密连接相互连接的特化上皮细胞组成的脑室结构，这些连接建立了血脑脊液（CSF）屏障。ChP 对于产生 CSF 和将溶质从脑内转运到脑外以及从脑外转运到脑内至关重要。ChP 功能和形态的恶化与神经退行性疾病的恶化有关。我们在此从年轻成年到 2 岁的小鼠中描绘了 ChP 上皮细胞在健康衰老过程中的形态功能变化。
我们使用了包括透射电子显微镜（TEM）、免疫组织化学、RT-qPCR、Western Blot 和多光子显微镜（2-PM）在内的多层次方法，在从年轻成年到 2 岁的多个时间点进行了研究。
我们从 8 至 12 个月大的小鼠中鉴定出 ChP 上皮细胞中存在明显的形态功能改变，这些改变在 2 岁之前基本保持稳定。这些变化包括上皮细胞扁平化、微绒毛长度减少和紧密连接中断增加。我们还发现老年小鼠中线粒体密度降低，线粒体伸长。在衰老的小鼠中，形态学上的线粒体重排伴随着超氧化物水平的增加、膜电位的降低和线粒体运动性的降低。有趣的是，大多数与年龄相关的变化并不伴随着蛋白和/或基因表达水平的改变，并且衰老的线粒体对急性药理应激刺激有有效反应。
我们的研究表明，在成年期，小鼠脉络丛上皮细胞的多种形态功能特征会发生长期进展，随后在衰老过程中会发生结构重塑。这些发现可以帮助我们更好地理解 ChP 在衰老过程中功能和形态变化的相关性。
