The choroid plexus maintains adult brain ventricles and subventricular zone neuroblast pool, which facilitates poststroke neurogenesis

• 成果类型: Article
• 署名作者: Taranov, Aleksandr; Bedolla, Alicia; Iwasawa, Eri; Brown, Farrah N.; Baumgartner, Sarah; Fugate, Elizabeth M.; Levoy, Joel; Crone, Steven A.; Goto, June; Luo, Yu
• 署名单位: University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; Cincinnati Children's Hospital Medical Center; University System of Ohio; University of Cincinnati
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8844
• DOI: 10.1073/pnas.2400213121
• 发表日期: 2024-07-09
• 关键词: cerebrospinal-fluid production; diphtheria-toxin; t-cells; SYSTEM; cns; pressure; ablation; ependyma; neurons; PATHWAY

摘要

The brain's neuroreparative capacity after injuries such as ischemic stroke is partly contained in the brain's neurogenic niches, primarily the subventricular zone (SVZ), which lies in close contact with the cerebrospinal fluid (CSF) produced by the choroid plexus (ChP). Despite the wide range of their proposed functions, the ChP/CSF remain among the most understudied compartments of the central nervous system (CNS). Here, we report a mouse genetic tool (the ROSA26iDTR mouse line) for noninvasive, specific, and temporally controllable ablation of CSF- producing ChP epithelial cells to assess the roles of the ChP and CSF in brain homeostasis and injury. Using this model, we demonstrate that ChP ablation causes rapid and permanent CSF volume loss in both aged and young adult brains, accompanied by disruption of ependymal cilia bundles. Surprisingly, ChP ablation did not result in overt neurological deficits at 1 mo postablation. However, we observed a pronounced decrease in the pool of SVZ neuroblasts (NBs) following ChP ablation, which occurs due to their enhanced migration into the olfactory bulb. In the middle cerebral artery occlusion model of ischemic stroke, NB migration into the lesion site was also reduced in the CSF- depleted mice. Thus, our study establishes an important role of ChP/CSF in regulating the regenerative capacity of the adult brain under normal conditions and after ischemic stroke.