Brain norepinephrine (NE) systems in rats, monkeys and humans, the locus coeruleus and its projections in particular, undergo degenerative changes during aging, as detected by morphological and biochemical methods. This probable decline in function of the NE system is exaggerated in the dementia of Alzheimers disease and Parkinsons disease. The proposed studies address the broad hypothesis that aging of the central NE system contributes to the expression of cognitive and memory deficits in some elderly individuals and in dementia. Specifically, aged Fischer-344 rats, screened for deficient performance of a spatial memory task (Morris water maze), will receive NE supplementation provided either by intracerebral implantation of fetal NE neurons, or chronic intraventricular infusion of NE via mini-pump. Control animals will receive no supplementation treatment or a graft of fetal cerebellar tissue. Efficacy of NE supplementation in memory- deficient aged rats will be assessed by re-testing behavior coupled with tests of the behavioral effects of drugs acting on the adrenergic system, and subsequent analysis of NE biochemistry and morphology in neural grafts and the host brain. These studies will provide further information on the state of brain NE systems in the rat model of behavioral senescence, the behavioral efficacy of chronic NE supplementation in these animals, the biochemical and morphological correlates of interactions between grafted NE neurons and the aged host brain, and whether the use of NE neuron grafts holds any promise as an experimental therapeutic approach for severe memory deficits in aging and dementia.
