The Role of PP2A Methylation in Susceptibility and Resistance to TBI and AD-Induced Neurodegeneration
Annual rept. 30 Sep 2012-29 Sep 2013
COLUMBIA UNIV NEW YORK
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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.
- Anatomy and Physiology
- Medicine and Medical Research