One of the most intriguing features of brain aging is the tremendous variability in the degree to which there is any loss of function. Certain individuals function alertly and show no loss of intellectual ability even into their 90's. In contrast, as early as their mid-5O's, others show memory disorders, language loss, disorientation, and in the extreme form, develop clinical dementias, such as Alzheimer's diseasee. What are the factors that might account for such impressive individual differences in brain aging? We are examining the way in which the hypothalamic-pituitary-adrenal (HPA) axis might regulate how the brain ages. There are at least two ways in which this might occur: Increased exposure to adrenal glucocorticoids in the aged rat might 1) accelerate or potentiate the loss of neurons and in doing so increase the loss of cognitive function, or 2) decrease the capacity of surviving cells to compensate for neuron loss, and this effect also appears to involve a loss of function. In these studies we are attempting relate changes in HPA activity to individual differences in hippocampal pathology in later life using animal models of both """"""""successful""""""""(i.e. the absence of hippocampal pathology and cognitive decline) and """"""""unsuccessful"""""""" aging. These experiments also involve long- itudinal studies in order to determine the temporal relationship between changes in HPA activity and hippocampal impairments. Do changes in HPA activity predict individual differences in the occurrence of hippocampal degeneration? We are also examining the relationship between increased HPA activity in later life and changes in other correlates of hippocampal pathology (e.g., decreased glucose utilization, changes in NMDA receptor bindin, neuron loss, changes in cholinergic systems,etc.). Is there an empirically valid profile of hippocampal decline and how is it related to changes in HPA activity? Finall, we are examining whether increased glucocorticoid levels in aged rats compromise function in the hippocampus using the long-term potentiation model of synaptic plasticity. Is it possible that increased glucocorticoid levels might not only potentiate the loss of hippocampal neurons, but also compromise function in remaining cells?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG009488-01
Application #
3121350
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1991-04-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Mcgill University
Department
Type
DUNS #
City
Montreal
State
PQ
Country
Canada
Zip Code
H3 0-G4
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