Exploring Synergies Among Neuronal Injury, Neurodegeneration, and Alzheimer s Disease with High-Throughput On-Chip Screening Platforms
Abstract
It is now known that traumatic brain injury (TBI) greatly increases the risk for Alzheimer s disease (AD) and other neurodegenerative diseases. Given that a large portion of the population, particularly veterans and former athletes, have suffered TBIs, understanding how TBI and AD are correlated is of utmost importance to identify efficient prevention and treatment strategies. However, understanding how TBI increases the risk of AD is a significant challenge, since identifying changes in form and function of the brain and neurons upon injury and the effect of those changes on risk of AD is unfeasible in humans and technically very difficult in mammalian model organisms. The work presented here will be focused on understanding how different patterns of injury result in adverse effects in the form and function of neurons and how these changes might accelerate the onset or progression of AD. Our work is based on using a well-known model organism: Caenorhabditis (C.) elegans, a small nematode that has been fundamental in our current knowledge of neuroscience and aging. We will develop controllable micro-devices capable of inducing injury in C. elegans neurons in the presence and absence of amyloid-beta, a peptide at the root of Alzheimer s disease pathology. We will characterize how different patterns of injury result in changes in neuronal shape and integrity, and the combined effects of injury and amyloid-beta peptides. In addition, using this platform, we will search for genes that affect the process upon which the presence of amyloid-beta potentiates the adverse effects of brain injury. The proposed work will provide a tool to perform experiments in a high-throughput fashion, and thus enable testing a large number of injury patterns to identify the most significant, as well as determining the most relevant genes involved in this process. The results from this study will be fundamental in understanding the biological processes affected in TBI and AD and will be fundamental for identifying potential treatment and prevention strategies.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810701
Entities
People
- Adriana San Miguel Delgadillo
Organizations
- North Carolina State University
- United States Army