Challenging epigenetic hallmarks of aging in the choroid plexus to improve brain homeostasis
The choroid plexus (CP) is a secretory tissue found in each of the brain ventricles. The CP produces a clear fluid called cerebrospinal fluid (CSF) which helps to cushion the brain, to circulate nutrients, and remove waste from our brain. In addition, the CP secretes important molecules involved in the production of new neurons in the adult brain, highlighting that the CP is important for repairing our brain. During aging, the CP exhibits a decline in all aspects of its functions, hence increasing the risk of developing age-related diseases such as Alzheimer’s disease.
We recently discovered that there is abnormal expression of factors that regulate gene expression (epigenetic factors) during CP aging. We hypothesized that this deregulation could lead to the aberrant expression of genes essential for CP functioning. We propose here to target these epigenetic factors with specific drugs and rescue a normal gene expression in the CP during aging. This study will investigate this potential by (1) characterizing epigenetic alterations that could explain the deregulation of gene expression, (2) screening for drugs that could improve gene expression and (3) confirming the implication of some specific epigenetic factors in CP aging. This project will address these objectives using the unique model of CP organoids derived from stem cells. The findings will provide a better understanding of the molecular mechanisms deregulated in the CP during aging. The successful identification of drugs will help preventing an accumulation of these alterations, improving brain functioning in late stages of life and hence offering a better quality of life at old age.
Benoit Laurent , Université de Sherbrooke
Partners and Donors
The Azrieli Foundation