Role of cholesterol metabolism in aging model of neuronal recovery
Description: Advancing age is a major risk factor for many neurodegenerative diseases, but the underlying mechanisms are not understood. The Crowston laboratory has recently demonstrated age-related impairment of neuronal recovery and associated increased neuronal death in an established optic nerve injury model. The predominant age-related changes were localized to excitatory synapses that activate ganglion cells in the retina. Because cholesterol is known to be important for synaptogenesis and recent evidence linking mutations in cholesterol metabolism with numerous neurodegenerative diseases, we hypothesize that age-related changes in cholesterol metabolism could be responsible for the observed defect in neuronal recovery through loss of synaptic plasticity. To test this hypothesis, experiments would be divided into two stages, a discovery stage and a hypothesis-driven stage. The aim of the discovery stage is to compare central nervous system (CNS) cholesterol metabolism in young versus aged animals, either with or without injury. If the hypothesis is correct, aged animals would be expected to have altered CNS cholesterol metabolism more susceptible to injury challenge. The hypothesis-driven stage is to then test how manipulating CNS cholesterol metabolism impacts synaptogenesis and recovery of visual function. This project will be done in collaboration with the Silver lab which has expertise in lipid transport and metabolism. Results would further our understanding of cholesterol metabolism in the aging CNS and how it impacts neuronal recovery.
Funder: Human Frontier Science Program
Amount:
Funding type: award
Start date: 2020-04-01
Investigator: Alvin Chun Yin KUK
Institution: National University of Singapore (acting through Duke-NUS Medical School)
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Funded outputs count: 0
Funder award ID: LT000733/2020-L
OpenAlex ID: G5848895253