In a wide range of species and tasks, aging is accompanied by a decreased capacity to remember new information. The major portion of this proposal is based on evidence relating circulating epinephrine and glucose to memory, cholinergic functions and brain 2-deoxyglucose (2-DG) uptake. 1. Epinephrine release after footshock is decreased in aged animals. 2. Epinephrine enhances memory in young animals by increasing circulating glucose levels. 3. Both epinephrine and glucose enhance memory in aged rodents, and glucose enhances memory in elderly humans. 4. Epinephrine and glucose augment a range of cholinergic functions in young animals. 5. Glucose injections increase brain 2-DG uptake in 2-yr-old and scopolamine- treated young mice. Experiments described here will examine the following issues. Expts. a.1- 4: Do decreases in circulating epinephrine and glucose predict the memory deficits observed in individual aged rats? Expts. b.1-4: Most findings suggest that cholinergic agonists readily enhance memory in young but not old animals. Are cholinergic agonists differentially effective in enhancing memory in both aged and young rats and mice? Do treatments (epinephrine, glucose, cholinergic agonists) which enhance memory in aged rodents augment brain 2-DG uptake? Are the effects of cholinergic agonists on memory (whether similar or different across ages) mediated by peripheral release of epinephrine and glucose? An additional recent finding is that age-related memory dysfunctions are most prominent in individual aged rat and human subjects with poor blood glucose control--i.e., a relatively large increase in blood glucose after glucose administration predicts poor memory in individual aged subjects. Comparable relationships are not seen in young adult animals or humans. Expts. c.1-2: In cross-sectional studies, at what age does the relationship between blood glucose control appear in rats and mice? In longitudinal studies, does blood glucose control in individual young rats and mice predict which individual animals will have memory deficits when they are old? In both the cross-sectional and longitudinal studies, similar questions will be asked regarding the relationship of blood glucose control and diminished responsiveness of epinephrine and glucose, as well as decreased brain 2-DG uptake.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG007648-02
Application #
3118828
Study Section
Psychobiology and Behavior Review Committee (PYB)
Project Start
1990-05-01
Project End
1995-04-30
Budget Start
1991-05-01
Budget End
1992-04-30
Support Year
2
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Maki, Agatha E; Morris, Kenneth A; Catherman, Kasia et al. (2014) Fibrinogen ?-chain-derived peptide is upregulated in hippocampus of rats exposed to acute morphine injection and spontaneous alternation testing. Pharmacol Res Perspect 2:e00037
Gold, Paul E; Korol, Donna L (2014) Forgetfulness during aging: an integrated biology. Neurobiol Learn Mem 112:130-8
Gold, Paul E (2014) Regulation of memory - from the adrenal medulla to liver to astrocytes to neurons. Brain Res Bull 105:25-35
Abbott, Sabra M; Arnold, Jennifer M; Chang, Qing et al. (2013) Signals from the brainstem sleep/wake centers regulate behavioral timing via the circadian clock. PLoS One 8:e70481
Morris, Ken A; Li, Sisi; Bui, Duat D et al. (2013) Glucose attenuates impairments in memory and CREB activation produced by an ?4?2 but not an ?7 nicotinic receptor antagonist. Neuropharmacology 67:233-42
Morris, Ken A; Gold, Paul E (2013) Epinephrine and glucose modulate training-related CREB phosphorylation in old rats: relationships to age-related memory impairments. Exp Gerontol 48:115-27
Morris, Ken A; Gold, Paul E (2012) Age-related impairments in memory and in CREB and pCREB expression in hippocampus and amygdala following inhibitory avoidance training. Mech Ageing Dev 133:291-9
Gold, Paul E; Wrenn, Sean M (2012) Cycloheximide impairs and enhances memory depending on dose and footshock intensity. Behav Brain Res 233:293-7
Sadowski, Renee N; Canal, Clint E; Gold, Paul E (2011) Lidocaine attenuates anisomycin-induced amnesia and release of norepinephrine in the amygdala. Neurobiol Learn Mem 96:136-42
Gold, P E; Countryman, R A; Dukala, D et al. (2011) Acetylcholine release in the hippocampus and prelimbic cortex during acquisition of a socially transmitted food preference. Neurobiol Learn Mem 96:498-503

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