The Role of PP2A Methylation in Susceptibility and Resistance to TBI and AD-Induced Neurodegeneration
Abstract
The focus of the current study is to test the effect of genetic manipulations that target the tau phosphatase, PP2A, on behavioral impairments resulting from shockwave exposure in a mouse model, and to compare those results with the effects of the same genetic manipulations on the sensitivity to AD-like impairments caused by acute beta-amyloid (A ) exposure. Our goal is to identify the molecular mechanisms that contribute to TBI or AD-related impairment so that this information can then be used to identify at-risk individuals and develop effective therapeutic approaches. The principal motivation behind this approach is the observation that aggregates of hyperphosphorylated tau are a common feature of multiple neurodegenerative conditions including Alzheimer s disease and traumatic brain injury-associated degeneration. We previously found that the two novel lines of transgenic mice will use in this study, altered sensitivity to A -induced electrophysiological and behavioral impairments, and our hypothesis is that they will exert similar effects on shocshockwave inducedairments. This effort has required a substantial investment in developing equipment and testing protocols for exposing mice to a range of shockwave exposure conditions that mimic militarily relevant exposures and then assessing the biochemical and behavioral consequences of those exposures. There is currently a pressing need for mouse models and methodologies that reproduce the key features of blast exposure observed in humans, and the results of our experiments are a significant contribution to that effort.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2013
- Accession Number
- ADA602077
Entities
People
- Barclay Morrison
- Christopher Hue
- Edward K Vogel
- Ottavio Arancio
- Russell Nicholls
Organizations
- Columbia University