Funding Agency:

National Institute of Health

Total Project Period:

2/15/09 - 1/31/14

Total Project Award:

$1,547,965

Principal Investigator:

C. Edward Dixon, PhD

Co-Investigator:

Larry Jenkins, PhD; Hong Yan, PhD

Project Summary:

This study will test the hypothesis that TBI causes dysfunction of the DARPP-32 phosphorylation in striato-cortical neurons which may contribute to alterations in ERK1/2 cascades and working memory deficits.

The project will measure the effects of TBI on this important intracellular signaling convergence point. The effects of TBI on dopamine receptor subtype 1 (D1) agonist-induced phosphorylation of DARPP-32 will be determined. Lastly, the project will determine if pharmacologic or genetic modulation of the phosphorylation at Thr34 and Thr75 of DARPP-32 can enhance posttraumatic neuronal survival and functional outcome.

The results of these studies will expand our knowledge of striato-cortical function after TBI and provide initial preclinical evidence to support clinical investigation targeting downstream biochemical pathways associated with DA agonist therapies for TBI. Our long-term goal is to develop new therapies to accelerate cognitive recovery following TBI.