Year: 2022
Type: dissertation
Abstract: The Choroid plexus (CP) is an epithelial tissue located in each brain ventricle. The CP plays a key role in maintaining the brain homeostasis by regulating important functions such as the production of the Cerebrospinal Fluid (CSF), the protection of the brain through the physical barrier called the Blood-CSF-Barrier (BCSFB), the removal of brain metabolites and the secretion of signaling molecules within the CSF. During aging, the CP shows a decline in its functions, increasing the risk of developing neurodegenerative diseases. The molecular mechanisms underlying the physiological changes are largely unknown. A former lab student has evaluated the impact of aging on the transcriptomic signature of the Lateral Ventricle Choroid Plexus (LVCP) collected from mice aged 6, 12, 18 and 24 months. The results showed two patterns of differential gene expression: some genes exhibit a gradual change in their expression from 6 to 24 months of age while other genes show an abrupt change of expression between 18 and 24 months. Gene ontology (GO) analyses show that genes whose expression decreases abruptly with age are involved in chromatin regulation, potentially directly linking CP aging to one of the main hallmarks of aging: epigenetic alterations. Further investigations are required to fully understand CP aging. The objective of this study was to address the age-related changes of other important molecules (chromatin and proteins) but also to identify the CP morphological changes during aging and verify whether they match pattern(s) in any of the layers of regulation (DNA, RNA, proteins). LVCPs were dissected from male and female C57/BL6 mice aged 6, 12, 18, and 24 months obtained from the Réseau Québécois de Recherche sur le Vieillissement (RQRV). The morphological study of the CP demonstrated that the basal membrane increased gradually during aging while the cells height and area were abruptly decreased at 24 months of age. We showed that changes in expression of chromatin regulators during aging are specific to the CP, affecting the regulation of specific histone modifications. Changes in the epigenetic landscape could directly deregulate the expression of genes essential for the optimal functioning of the CP-CSF system. We confirmed by immunofluorescence that the integrity of the BCSFB and the production of CSF were perturbed at 24 months old. We also showed that the CP secretome exhibited important changes at various ages. Our findings provide a better understanding of the molecular mechanisms that underlie CP aging and could help the identification of therapeutic solutions to improve healthy aging and forestall the onset of neurodegenerative diseases.
Author: Avila Lopez, Jessica
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7201920644