Modifications de la signature transcriptomique du plexus choroïde pendant le vieillissement chez les souris
Year: 2020
Type: dissertation
Abstract: The choroid plexus (CP) is an epithelial tissue located in each of the ventricles of the brain (lateral, third and fourth ventricles) and where it sits on a stroma like-bed above a network of fenestrated blood capillaries. Water, nutrients and other substances are filtered from the blood into the brain’s ventricles through the CP epithelium to produce the cerebrospinal fluid (CSF). The CP-CSF system is crucial for the protection and maintenance of brain homeostasis. The CP also plays an active role in the development and repair of the brain. It is strategically positioned within the ventricles to secrete active key molecules, some of them being important for the proliferation of neural stem cells in the developing and adult brain. Throughout the lifespan, the CP goes through a natural and gradual aging process in which there are morphological changes in the tissue. These modifications alter the CP functionality, such as the filtering and secreting properties. However, it is not clear whether these changes occur progressively during aging. The goal of this study is to characterize the impact of aging on the transcriptomic signature of the CP. Lateral Ventricle Choroid Plexus (LVCP) tissue was micro-dissected and collected from mice aged 6, 12, 18 and 24 months available through the RQRV (Réseau Québécois de Recherche sur le Vieillissement). RNA sequencing was performed to establish gene-expression profiling and evaluate the transcriptomic differences in the LVCP over the mouse lifespan. We found two patterns of differential gene expression during CP aging. Some genes exhibited a gradual increase or decrease of their expression from 6 months to 24 months of age while other genes showed an abrupt increase or decrease of expression between 18 months and 24 months of age. Gene ontology analysis indicated a decrease of genes involved in important brain functions during aging (i.e. generation of neurons, metal ion transport, synaptic transmission), while genes that show an upregulation are involved in immune responses, confirming results previously described in the literature. We also specifically looked at the genes involved in the CP regulatory functions and showed that 61% of genes involved in the production of CSF exhibit a decline of their expression during aging. However, we found that the 37 genes involved in the maintenance of the blood-CSF-barrier remain relatively stable during aging. We also observed that genes that are highly expressed by the CP remain stable in their level of expression during aging, suggesting that there are important mechanisms maintaining these genes intact during aging. Together, our results showed aging-dependent variations in the expression of genes that play a vital role in CP physiology and functioning. We identified important sets of genes that could play an essential role in brain homeostasis. This study could potentially function as the first step to determine, in future studies, whether the decline of some cerebral functions can be linked to abnormal physiology of the CP.
Author: Rocha Ahumada, Javier
Institution: Université de Sherbrooke
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7201932600