We are characterizing the CNS phenotypes caused by elevated mtDNA mutation levels and relating these findings to age-related functional changes. Furthermore, we will investigate the affects of ischemic brain injury in these same mice. We have already documented change in cortical thickness and lamination patterns. There are also changes in oxidative energy production and mitochondrial function. These changes parallel cognitive and motor deficiencies in the mtDNA mutators. Drugs that upregulate mitochondrial function are being evaluated.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$199,631
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
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Good, Cameron H; Hoffman, Alexander F; Hoffer, Barry J et al. (2011) Impaired nigrostriatal function precedes behavioral deficits in a genetic mitochondrial model of Parkinson's disease. FASEB J 25:1333-44
Harvey, Brandon K; Richie, Christopher T; Hoffer, Barry J et al. (2011) Transgenic animal models of neurodegeneration based on human genetic studies. J Neural Transm (Vienna) 118:27-45