Determine whether overexpression of the gene for glutamate dehydrogenase 1 (GLUD1) in neurons of the CNS causes neurodegeneration, produces the characteristics of glutamate-induced excitotoxicity and oxidative stress, and diminishes the longevity of Tg as compared with wt mice.
Determine if GLUD1 Tg mice exhibit the neurochemical characteristics observed in states of glutamate excitotoxicity or those expected to be observed in such states.
Determine if calorie restriction decreases the neurodegeneration and increases the longevity of GLUD1 Tg and wt mice.
Identify the changes in gene transcription and protein levels occurring in neurons and glia of the frontal cortex in response to lifelong exposure to elevated glutamate levels.
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