Rescue of Abeta(1-42)-induced memory impairment in day-old chick by facilitation of astrocytic oxidative metabolism: implications for Alzheimer's disease.

Full Abstract

Administration of small oligomeric beta-amyloid (Abeta)(1-42) 45 min before one-trial bead discrimination learning in day-old chicks abolishes consolidation of learning 30 min post-training (Gibbs et al. Neurobiol. Aging, in press). Administration of the beta3-adrenergic agonist CL316243, which specifically stimulates astrocytic but not neuronal glucose uptake, rescues Abeta impaired memory. Weakly reinforced training can be consolidated by various metabolic substrates and we have demonstrated neuronal dependence on oxidative metabolism of glucose soon after training versus astrocytic glucose dependence 20 min later. Based on these findings we examined whether different metabolic substrates were able to counteract memory inhibition by Abeta(1-42). Although lactate, the medium-chain fatty acid octanoate, and the ketone body beta-hydroxybutyrate consolidated weakly reinforced training when injected close to learning, none of them were able to salvage Abeta-impaired memory; at this early time. All three metabolites and the astrocytic-specific acetate consolidated weak learning and rescued Abeta-impaired memory when injected 10-20 min post-training. However, neither glucose nor insulin rescued memory when injected at 20 min. Rescue of memory by providing astrocytes with alternative substrates for oxidative metabolism suggests that Abeta(1-42) exerts its amnestic effects specifically by impairing astrocytic glycolysis.

Author information

Author/s: Gibbs, Marie E (ME); Gibbs, Zoe (Z); Hertz, Leif (L);

Affiliation: Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia. marie.gibbs(-atsign-)med.monash.edu.au

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of neurochemistry (J Neurochem), published in England. (Language: eng)

Reference: 2009-May; vol 109 Suppl 1 (issue ) : pp 230-6

Dates: Created 2009/04/27; Completed 2009/05/21;

PMID: 19393032, status: MEDLINE (last retrieval date: 5/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

3-Hydroxybutyric Acid - metabolism
Acetates - pharmacology
Alzheimer Disease - metabolism; psychology
Amyloid beta-Protein - antagonists & inhibitors; toxicity
Animals
Animals, Newborn
Astrocytes - drug effects; metabolism
Chickens - physiology
Citric Acid Cycle - drug effects
Discrimination Learning - drug effects

Glucose - metabolism; pharmacology
Hypoglycemic Agents - pharmacology
Insulin - pharmacology
Ketone Bodies - metabolism
Lactic Acid - metabolism
Memory Disorders - chemically induced; psychology
Octanoic Acids - pharmacology
Oxidation-Reduction
Peptide Fragments - antagonists & inhibitors; toxicity
Reinforcement (Psychology)

Associated Chemicals: Acetates (0) ; Amyloid beta-Protein (0) ; Hypoglycemic Agents (0) ; Ketone Bodies (0) ; Octanoic Acids (0) ; Peptide Fragments (0) ; amyloid beta-protein (1-42) (0) ; Insulin (11061-68-0) ; caprylic acid (124-07-2) ; 3-Hydroxybutyric Acid (300-85-6) ; Lactic Acid (50-21-5) ; Glucose (50-99-7)

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