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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AG008133-05
Application #
3453291
Study Section
Biopsychology Study Section (BPO)
Project Start
1988-12-01
Project End
1993-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
5
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
Collier, Timothy J; Greene, James G; Felten, David L et al. (2004) Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats. Neurobiol Aging 25:209-21
Collier, Timothy J; Steece-Collier, Kathy; McGuire, Susan et al. (2003) Cellular models to study dopaminergic injury responses. Ann N Y Acad Sci 991:140-51
Collier, T J; Springer, J E (1994) Neural graft augmentation through co-grafting: implantation of cells as sources of survival and growth factors. Prog Neurobiol 44:309-31
Collier, T J; Martin, P N (1993) Schwann cells as a source of neurotrophic activity for dopamine neurons. Exp Neurol 124:129-33
Collier, T J; Coleman, P D (1991) Divergence of biological and chronological aging: evidence from rodent studies. Neurobiol Aging 12:685-93
Collier, T J; Springer, J E (1991) Co-grafts of embryonic dopamine neurons and adult sciatic nerve into the denervated striatum enhance behavioral and morphological recovery in rats. Exp Neurol 114:343-50
Pearlman, S H; Levivier, M; Collier, T J et al. (1991) Striatal implants protect the host striatum against quinolinic acid toxicity. Exp Brain Res 84:303-10
Collier, T J; Sladek, C D; Gallagher, M J et al. (1990) Diffusible factor(s) from adult rat sciatic nerve increases cell number and neurite outgrowth of cultured embryonic ventral mesencephalic tyrosine hydroxylase-positive neurons. J Neurosci Res 27:394-9